Imidazopyridines for the treatment of neurological disorders

ABSTRACT

Corticotropin releasing factor (CRF) antagonists of formula (I):                    
     and their use in treating psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.

This application is a continuation of U.S. Ser. No. 09/109,877, filed Jul. 2, 1998, which-in-turn claims the benefit of U.S. Provisional Application Ser. Nos. 60/051,628, filed Jul. 3, 1997 and 60/080,665, filed Apr. 3, 1998.

FIELD OF THE INVENTION

The present invention relates to novel compounds, compositions, and methods for the treatment of psychiatric disorders and neurological diseases, including major depression, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders, as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress. In particular, the present invention relates to novel imidazopyrimidines and imidazopyridines, pharmaceutical compositions containing such compounds and their use in treating psychiatric disorders, neurological diseases, immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.

BACKGROUND OF THE INVENTION

Corticotropin releasing factor (herein referred to as CRF), a 41 amino acid peptide, is the primary physiological regulator of proopiomelanocortin (POMC)—derived peptide secretion from the anterior pituitary gland [J. Rivier et al., Proc. Nat. Acad. Sci. (USA) 80:4851 (1983); W. Vale et al., Science 213:1394 (1981)]. In addition to its endocrine role at the pituitary gland, immunohistochemical localization of CRF has demonstrated that the hormone has a broad extrahypothalamic distribution in the central nervous system and produces a wide spectrum of autonomic, electrophysiological and behavioral effects consistent with a neurotransmitter or neuromodulator role in brain [W. Vale et al., Rec. Prog. Horm. Res. 39:245 (1983); G. F. Koob, Persp. Behav. Med. 2:39 (1985); E. B. De Souza et al., J. Neurosci. 5:3189 (1985)]. There is also evidence that CRF plays a significant role in integrating the response of the immune system to physiological, psychological, and immunological stressors [J. E. Blalock, Physiological Reviews 69:1 (1989); J. E. Morley, Life Sci. 41:527 (1987)].

Clinical data provide evidence that CRF has a role in psychiatric disorders and neurological diseases including depression, anxiety-related disorders and feeding disorders. A role for CRF has also been postulated in the etiology and pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, progressive supranuclear palsy and amyotrophic lateral sclerosis as they relate to the dysfunction of CRF neurons in the central nervous system [for review see E. B. De Souza, Hosp. Practice 23:59 (1988)].

In affective disorder, or major depression, the concentration of CRF is significantly increased in the cerebral spinal fluid (CSF) of drug-free individuals [C. B. Nemeroff et al., Science 226:1342 (1984); C. M. Banki et al., Am. J. Psychiatry 144:873 (1987); R. D. France et al., Biol. Psychiatry 28:86 (1988); M. Arato et al., Biol Psychiatry 25:355 (1989)]. Furthermore, the density of CRF receptors is significantly decreased in the frontal cortex of suicide victims, consistent with a hypersecretion of CRF [C. B. Nemeroff et al., Arch. Gen. Psychiatry 45:577 (1988)]. In addition, there is a blunted adrenocorticotropin (ACTH) response to CRF (i.v. administered) observed in depressed patients [P. W. Gold et al., Am J. Psychiatry 141:619 (1984); F. Holsboer et al., Psychoneuroendocrinology 9:147 (1984); P. W. Gold et al., New Eng. J. Med. 314:1129 (1986)]. Preclinical studies in rats and non-human primates provide additional support for the hypothesis that hypersecretion of CRF may be involved in the symptoms seen in human depression [R. M. Sapolsky, Arch. Gen. Psychiatry 46:1047 (1989)]. There is preliminary evidence that tricyclic antidepressants can alter CRF levels and thus modulate the numbers of CRF receptors in brain [Grigoriadis et al., Neuropsychopharmacology 2:53 (1989)].

It has also been postulated that CRF has a role in the etiology of anxiety-related disorders. CRF produces anxiogenic effects in animals and interactions between benzodiazepine/non-benzodiazepine anxiolytics and CRF have been demonstrated in a variety of behavioral anxiety models [D. R. Britton et al., Life Sci. 31:363 (1982); C. W. Berridge and A. J. Dunn Regul. Peptides 16:83 (1986)]. Preliminary studies using the putative CRF receptor antagonist a-helical ovine CRF (9-41) in a variety of behavioral paradigms demonstrate that the antagonist produces “anxiolytic-like” effects that are qualitatively similar to the benzodiazepines [C. W. Berridge and A. J. Dunn Horm. Behav. 21:393 (1987), Brain Research Reviews 15:71 (1990)].

Neurochemical, endocrine and receptor binding studies have all demonstrated interactions between CRF and benzodiazepine anxiolytics, providing further evidence for the involvement of CRF in these disorders. Chlordiazepoxide attenuates the “anxiogenic” effects of CRF in both the conflict test [K. T. Britton et al., Psychopharmacology 86:170 (1985); K. T. Britton et al., Psychopharmacology 94:306 (1988)] and in the acoustic startle test [N. R. Swerdlow et al., Psychopharmacology 88:147 (1986)] in rats. The benzodiazepine receptor antagonist (Rol5-1788), which was without behavioral activity alone in the operant conflict test, reversed the effects of CRF in a dose-dependent manner while the benzodiazepine inverse agonist (FG7142) enhanced the actions of CRF [K. T. Britton et al., Psychopharmacology 94:306 (1988)].

It has been further postulated that CRF has a role in immunological, cardiovascular or heart-related diseases such as hypertension, tachycardia and congestive heart failure, stroke, osteoporosis, premature birth, psychosocial dwarfism, stress-induced fever, ulcer, diarrhea, post-operative ileus and colonic hypersensitivity associated with psychopathological disturbance and stress.

The mechanisms and sites of action through which the standard anxiolytics and antidepressants produce their therapeutic effects remain to be elucidated. It has been hypothesized however, that they are involved in the suppression of the CRF hypersecretion that is observed in these disorders. Of particular interest is that preliminary studies examining the effects of a CRF receptor antagonist (a-helical CRF9-41) in a variety of behavioral paradigms have demonstrated that the CRF antagonist produces “anxiolytic-like” effects qualitatively similar to the benzodiazepines [for review see G. F. Koob and K. T. Britton, In: Corticotropin-Releasing Factor: Basic and Clinical Studies of a Neuropeptide, E. B. De Souza and C. B. Nemeroff eds., CRC Press p221 (1990)].

DuPont Merck PCT application US94/11050 describes corticotropin releasing factor antagonist compounds of the formula:

and their use to treat psychiatric disorders and neurological diseases. Included in the description are fused pyridines and pyrimidines of the formula:

where: V is CR^(1a) or N; Z is CR² or N; A is CR³O or N; and D is CR²⁸ or N.

Other compounds reported to have activity as corticotropin releasing factors are disclosed in WO 95/33750, WO 95/34563 and WO 95/33727.

SUMMARY OF THE INVENTION

In accordance with one aspect, the present invention provides novel compounds which bind to corticotropin releasing factor receptors, thereby altering the anxiogenic effects of CRF secretion. The compounds of the present invention are useful for the treatment of psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.

According to another aspect, the present invention provides novel compounds of formula (I) (described below) which are useful as antagonists of the corticotropin releasing factor. The compounds of the present invention exhibit activity as corticotropin releasing factor antagonists and appear to suppress CRF hypersecretion. The present invention also includes pharmaceutical compositions containing such compounds of formula (I), and methods of using such compounds for the suppression of CRF hypersecretion, and/or for the treatment of anxiogenic disorders.

According to yet another aspect, the present invention provides novel compounds, pharmaceutical compositions and methods which may be used in the treatment of affective disorder, anxiety, depression, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal disease, anorexia nervosa or other feeding disorder, drug or alcohol withdrawal symptoms, drug addiction, inflammatory disorder, fertility problems, disorders, the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, or a disorder selected from inflammatory disorders such as rheumatoid arthritis and osteoarthritis, pain, asthma, psoriasis and allergies; generalized anxiety disorder; panic, phobias, obsessive-compulsive disorder; post-traumatic stress disorder; sleep disorders induced by stress; pain perception such as fibromyalgia; mood disorders such as depression, including major depression, single episode depression, recurrent depression, child abuse induced depression, and postpartum depression; dysthemia; bipolar disorders; cyclothymia; fatigue syndrome; stress-induced headache; cancer, human immunodeficiency virus (HIV) infections; neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease; gastrointestinal diseases such as ulcers, irritable bowel syndrome, Crohn's disease, spastic colon, diarrhea, and post operative ilius and colonic hypersensitivity associated by psychopathological disturbances or stress; eating disorders such as anorexia and bulimia nervosa; hemorrhagic stress; stress-induced psychotic episodes; euthyroid sick syndrome; syndrome of inappropriate antidiarrhetic hormone (ADH); obesity; infertility; head traumas; spinal cord trauma; ischemic neuronal damage (e.g., cerebral ischemia such as cerebral hippocampal ischemia); excitotoxic neuronal damage; epilepsy; cardiovascular and hear related disorders including hypertension, tachycardia and congestive heart failure; stroke; immune dysfunctions including stress induced immune dysfunctions (e.g., stress induced fevers, porcine stress syndrome, bovine shipping fever, equine paroxysmal fibrillation, and dysfunctions induced by confinement in chickens, sheering stress in sheep or human-animal interaction related stress in dogs); muscular spasms; urinary incontinence; senile dementia of the Alzheimer's type; multiinfarct dementia; amyotrophic lateral sclerosis; chemical dependencies and addictions (e.g., dependencies on alcohol, cocaine, heroin, benzodiazepines, or other drugs); drug and alcohol withdrawal symptoms; osteoporosis; psychosocial dwarfism and hypoglycemia in mammals.

According to a still further aspect of the invention, the compounds provided by this invention (and especially labelled compounds of this invention) are also useful as standards and reagents in determining the ability of a potential pharmaceutical to bind to the CRF receptor.

DETAILED DESCRIPTION OF INVENTION

[1] Thus, in a first embodiment, the present invention provides a novel compound of formula I:

or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:

A is N or C—R⁷;

B is N or C—R⁸;

provided that at least one of the groups A and B is N;

D is an aryl or heteroaryl group attached through an unsaturated carbon atom;

X is selected from the group CH—R⁹, N—R¹⁰, O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl, C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, —SO₂—C₁₋₁₀ alkyl, —SO₂—R^(1a), and —SO₂—R^(1b);

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R¹ is also substituted with 0-3 substituents independently selected at each occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), —NR^(13a)R^(16a), C₁₋₄ alkoxy-C₁₋₄ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than:

(a) a cyclohexyl-(CH₂)₂— group;

(b) a 3-cyclopropyl-3-methoxypropyl group;

(c) an unsubstituted-(alkoxy)methyl group; and,

(d) a 1-hydroxyalkyl group;

also provided that when R¹ alkyl substituted with OH, then the carbon adjacent to the ring N is other than CH₂;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R^(1c) is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR^(13a), SH, —S(O)_(n)R^(14a), —COR^(13a), —OC(O)R^(14b), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b) and wherein any sulfur atom is optionally monooxidized or dioxidized;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl, —(CH₂)₁₋₄-heteroaryl, or —(CH₂)₁₋₄-heterocycle, wherein the aryl, heteroaryl, or heterocycle group is substituted or unsubstituted;

R² is selected from the group C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-3 substituents selected from the group —CN, hydroxy, halo and C₁₋₄ alkoxy;

alternatively R², in the case where X is a bond, is selected from the group —CN, CF₃ and C₂F₅;

R³, R⁷ and R⁸ are independently selected at each occurrence from the group H, Br, Cl, F, I, —CN, C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, C₁₋₄ alkylsulfinyl, C₁₋₄ alkylsulfonyl, amino, C₁₋₄ alkylamino, (C₁₋₄ alkyl)₂amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group C₁₋₇ alkyl, C₃₋₈ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, C₁₋₄ alkylthio, C₁₋₄ alkyl sulfinyl, C₁₋₄ alkylsulfonyl, C₁₋₆ alkylamino and (C₁₋₄ alkyl)₂amino;

provided that when R¹ is unsubstituted C₁₋₁₀ alkyl, then R³ is other than substituted or unsubstituted phenyl;

R⁹ and R¹⁰ are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl-C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl, aryl(C₁₋₄ alkyl)-, heteroaryl and heteroaryl(C₁₋₄ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl, aryl(C₁₋₄ alkyl)-, heteroaryl and heteroaryl(C₁₋₄ alkyl)- and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy C₁₋₄ haloalkoxy, and dimethylamino;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C³⁻⁷ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷ is selected at each occurrence from the group H, C¹⁻⁶ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₁₋₄ haloalkyl, R¹⁴S(O)_(n)—C₁₋₄ alkyl, and R^(17b)R^(19b)N—C₂₋₄ alkyl;

R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, if an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

alternatively, in an NR^(17b)R^(19b) moiety, R^(17b) and R^(19b) taken together form 1-pyrrolidinyl 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR₁₄ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is independently selected at each occurrence from the group phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, methylenedioxy, C₁₋₄ alkoxy-C₁₋₄ alkoxy, —OR¹⁷, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, —NO₂, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and up to 1 phenyl, each phenyl substituent being substituted with 0-4 substituents selected from the group C₁₋₃ alkyl, C₁₋₃ alkoxy, Br, Cl, F, I, —CN, dimethylamino, CF₃, C₂F₅, OCF₃, SO₂Me and acetyl;

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a); and,

provided that when D is imidazole or triazole, R¹ is other than unsubstituted C₁₋₆ linear or branched alkyl or C₃₋₆ cycloalkyl.

[2] In a preferred embodiment, the present invention provides a novel compound of formula Ia:

[2a] In a more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, and C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl and indanyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-1 substituents selected from the group —CN, OH, Cl, F, and C₁₋₄ alkoxy;

R³ and R⁸ are independently selected at each occurrence from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[2b] In an even more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted C₁₋₆ alkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁸ are independently selected at each occurrence from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[2c] In a still more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

R¹ is substituted C₁;

R¹ is substituted with 0-1 substituents selected from the group —CN, —CO₂CH₃, and —CO₂CH₂CH₃;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl, CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁸ are independently selected at each occurrence from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[2d] In a further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

R¹ is substituted (cyclopropyl)-C₁ alkyl or (cyclobutyl)-C₁ alkyl;

R¹ is substituted with 0-1 —CN;

R¹ is also substituted with 0-1 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[2e] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)-C₁ alkyl substituted with 1 substituent independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, Cl, F, and CF₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, and isoxazolyl, each heteroaryl being substituted on 0-2 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, OCH₃, Cl, F, and CF₃.

[2f] In an even further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

R¹ is selected from the group (cyclopropyl)CH—CH₃, (cyclopropyl)CH—CH₂CH₃, (cyclopropyl)CH—CH₂OCH₃, (cyclopropyl)CH—CH₂CH₂CH₃, (cyclopropyl)CH—CH₂CH₂OCH₃, (cyclopropyl)₂CH, phenyl(cyclopropyl)CH, furanyl(cyclopropyl)CH, thienyl(cyclopropyl)CH, isoxazolyl(cyclopropyl)CH, (CH₃-furanyl)(cyclopropyl)CH, (cyclobutyl)CH—CH₃, (cyclobutyl)CH—CH₂CH₃, (cyclobutyl)CH—CH₂OCH₃, (cyclobutyl)CH—CH₂CH₂CH₃, (cyclobultyl)CH—CH₂CH₂OCH₃, (cyclobutyl)2CH, phenyl(cyclobutyl)CH, furanyl(cyclobutyl)CH, thienyl(cyclobutyl)CH, isoxazolyl(cyclobutyl)CH, and (CH₃-furanyl)(cyclobutyl)CH;

[2g] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[2h] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[2i] In another preferred embodiment, the present invention provides a novel compound of formula Ia, wherein the compound is selected from the group:

3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-(methylsulfanyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-cyclopropylpropyl)-2-(methylsulfanyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-ethyl-7-[2-methyl-4-(trifluoromethyl)phenyl]-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-ethyl-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-fluoro-4-methoxyphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methylphenyl)-3-(1-cyclopropylpropyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-fluoro-4-methylphenyl)-3-(1-cyclopropylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-ethyl-7-(2,4,5-trimethylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-methoxy-7-(2,4,5-trimethylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-ethyl-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-2-methoxy-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-7-(2,6-dimethyl-3-pyridinyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

3-(1-cyclopropylpropyl)-7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b pyridine;

5 7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(methylsulfonyl)phenyl]-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethylpropyl)-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethylpropyl)-2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethylpropyl)-7-[4-methoxy-2-(trifluoromethyl)phenyl]-3H-imidazo[4,5-b]pyridine;

3-(1-ethylpropyl)-2-methoxy-7-[4-methoxy-2-(trifluoromethyl)phenyl]-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethylpropyl)-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethylpropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethylpropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

3-chloro-4-[2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridin-7-yl]benzonitrile;

3-chloro-4-[3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]benzonitrile;

1-{3-chloro-4-[2-ethyl-3-(1-ethylpropyl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;

1-{3-chloro-4-(3-(1-ethylpropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;

3-(dicyclopropylmethyl)-2-ethyl-7-(5-fluoro-4-methoxy-2-methylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(dicyclopropylmethyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(dicyclopropylmethyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(dicyclopropylmethyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-3-(dicyclopropylmethyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-3-(dicyclopropylmethyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(dicyclopropylmethyl)-2-ethyl-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(dicyclopropylmethyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-4-methoxyphenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methoxyphenyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methoxyphenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethyl-3-methoxypropyl)-2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethyl-3-methoxypropyl)-7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methylphenl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methylphenyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(methylsulfonyl)phenyl]-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

1-{3-chloro-4-[2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;

1-{3-chloro-4-[3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]phenyl}-1-ethanone;

1-{5-[2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridin-7-yl]-6-methyl-2-pyridinyl}-1-ethanone;

1-{5-[3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridin-7-yl]-6-methyl-2-pyridinyl}-1-ethanone;

2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethyl-3-methoxypropyl)-2-methoxy-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethoxy-3-pyridinyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3-(1-ethyl-3-methoxypropyl)-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethyl-3-pyridinyl)-3-(1-ethyl-3-methoxypropyl)-2-methoxy-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-(1-ethyl-3-methoxypropyl)-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

3-(1-ethyl-3-methoxypropyl)-2-methoxy-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2,4-dichlorophenyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(trifluoromethyl)phenyl]-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methylphenyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2-chloro-5-fluoro-4-methylphenyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

2-ethyl-7-(4-methoxy-2,5-dimethylphenyl)-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

2-methoxy-7-(4-methoxy-2,5-dimethylphenyl)-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

2-ethyl-7-(5-fluoro-4-methoxy-2-methylphenyl)-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-[1-(methoxymethyl)propyl]-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

2-methoxy-3-[1-(methoxymethyl)propyl]-7-(6-methoxy-2-methyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethoxy-3-pyridinyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2,6-dimethyl-3-pyridinyl)-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

7-(2, 6-dimethyl-3-pyridinyl)-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

2-ethyl-3-[1-(methoxymethyl)propyl]-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

2-methoxy-3-[1-(methoxymethyl)propyl]-7-(2,5,6-trimethyl-3-pyridinyl)-3H-imidazo[4,5-b]pyridine;

7-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine; and

7-[2-chloro-4-(methylsulfonyl)phenyl]-2-methoxy-3-[1-(methoxymethyl)propyl]-3H-imidazo[4,5-b]pyridine;

or a pharmaceutically acceptable salt form thereof.

[2j] In another more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

R¹ is C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), NR^(15a)CO₂R^(14b), —CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R¹ is also substituted with 0-3 substituents independently selected at each occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and —NR^(13a)R^(16a).

[2k] In another even more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group cyclopropyl, cyclobutyl, and cyclopentyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₄₋₈ cycloalkyl, wherein one carbon atom in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—;

R is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and —NR^(13a)R^(16a);

R^(1a) is aryl and is selected from the group phenyl and indanyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-1 substituents selected from the group —CN, OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R³ and R⁸ are independently selected at each occurrence from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[2l] In another still more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted with 0-1 substituents selected from the group —CN, —CO₂R^(13a), and C₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₃, —OR^(13a), —OH, —OCH₃, —OCH₂CH₃, —CH₂OCH₃, —CH₂CH₂OCH₃, and —NR^(13a)R^(16a);

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁸ are independently selected at each occurrence from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[2m] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

R¹ is substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, and CF₃;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon-atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁸ are independently selected at each occurrence from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[2n] In another even further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

R¹ is substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃—, CH₃, —CO₂OCH₃, —CH₂CH₂OCH₃, F, and CF₃; and,

R^(1a) is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[2o] In a still further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[2p] In another still further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[2q] In another more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀alkynyl, C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ alkoxy-C₁₋₄ alkyl;

R¹ is substituted with a C₃₋₈ cycloalkyl group, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl group is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR— and —NSO₂R^(14b)—;

R¹ is also substituted with 0-3 substituents independently selected at each occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R^(1c) is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR^(13a), SH, S(O)_(n)R^(14b), —COR^(13a), —OC(O)R^(14b), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b) and wherein any sulfur atom is optionally monooxidized or dioxidized.

[2r] In another even more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, and C₃₋₈ cycloalkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl group, wherein 0-1 carbon atoms in the C₄₋₆ cycloalkyl group is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

R^(1a) is aryl and is selected from the group phenyl and indanyl, each R¹a being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-1 substituents selected from the group —CN, OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R³ and R⁸ are independently selected at each occurrence from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[2s] In another still more preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

X is selected from the group O, S and a bond;

R¹ is C₁₋₆ alkyl;

R is substituted with a C₃₋₆ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₆ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, F, CF₃, —OR^(13a), —NR^(13a)R^(16a), —CH₂OCH₃, —CH₂CH₂OCH₃, and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁸ are independently selected at each occurrence from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[2t] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl, CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁸ are independently selected at each occurrence from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[2u] In another even further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[2v] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[2w] In another further preferred embodiment, the present invention provides a novel compound of formula Ia, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[3] In another preferred embodiment, the present invention provides a novel compound of formula Ib:

[3a] In another more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, and C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl and indanyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-1 substituents selected from the group —CN, OH, Cl, F, and C₁₋₄ alkoxy;

R³ and R⁷ are independently selected at each occurrence from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[3b] In another even more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted C₁₋₆ alkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, —OR^(13a), NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁷ are independently selected at each occurrence from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[3c] In another still more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

R¹ is substituted C₁;

R¹ is substituted with 0-1 substituents selected from the group —CN, —CO₂CH₃, and —CO₂CH₂CH₃;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl, CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁷ are independently selected at each occurrence from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[3d] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

R¹ is substituted (cyclopropyl)-C₁ alkyl or (cyclobutyl)-C₁ alkyl;

R¹ is substituted with 0-1 —CN;

R¹ is also substituted with 0-1 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), Br, Cl, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R¹ is also substituted with 0-1 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[3e] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)-C₁ alkyl substituted with 1 substituent independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, Cl, F, and CF₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, and isoxazolyl, each heteroaryl being substituted on 0-2 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, OCH₃, Cl, F, and CF₃.

[3f] In an even further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

R¹ is selected from the group (cyclopropyl)CH—CH₃, (cyclopropyl)CH—CH₂CH₃, (cyclopropyl))CH—CH₂OCH₁₃, (cyclopropyl)CH—CH₂CH₂CH₃, (cyclopropyl)CH—CH₂CH₂OCH₃, (cyclopropyl)₂CH, phenyl(cyclopropyl)CH, furanyl(cyclopropyl)CH, thienyl(cyclopropyl)CH, isoxazolyl(cyclopropyl)CH, (CH₃-furanyl)(cyclopropyl)CH, (cyclobutyl)CH—CH₃, (cyclobutyl)CH—CH₂CH₃, (cyclobutyl)CH—CH₂OCH₃, (cyclobutyl)CH—CH₂CH₂CH₃, (cyclobutyl)CH—CH₂CH₂OCH₃, (cyclobutyl)₂CH, phenyl(cyclobutyl)CH, furanyl(cyclobutyl)CH, thienyl(cyclobutyl)CH, isoxazolyl(cyclobutyl)CH, and (CH₃-furanyl)(cyclobutyl)CH;

[3g] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[3h] in another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[3i] In another preferred embodiment, the present invention provides a novel compound of formula Ib, wherein the compound is selected from the group:

1-(1-cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-ethyl-1H-imidazo [4,5-c]pyridine;

1-(1-cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-ethyl-4-[2-methyl-4-(trifluoromethyl)phenyl]-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-cyclopropylpropyl)-2-(methylsulfanyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-ethyl-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-fluoro-4-methoxyphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methylphenyl)-1-(1-cyclopropylpropyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

2,4-(2-chloro-fluoro-4-methylphenyl)-1-(1-cyclopropylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-methoxy-4-(2,4,5-trimethylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-ethyl-4-(2,4,5-trimethylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-2-ethyl-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine

1-(1-cyclopropylpropyl)-2-methoxy-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-4-(2,6-dimethyl-3-pyridinyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-4-(2,6-dimethyl-3-pyridinyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

1-(1-cyclopropylpropyl)-4-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(methylsulfonyl)phenyl]-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethylpropyl)-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(1-ethylpropyl)-2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethylpropyl)-4-[4-methoxy-2-(trifluoromethyl)phenyl]-1H-imidazo[4,5-c]pyridine;

1-(1-ethylpropyl)-2-methoxy-4-[4-methoxy-2-(trifluoromethyl)phenyl]-1H-imidazo[4,5-c]pyridine;

1-(1-ethylpropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethylpropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-1H-imidazo[4,5-c]pyridine;

3-chloro-4-[1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]benzonitrile;

3-chloro-4-[2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridin-4-yl]benzonitrile;

1-{3-chloro-4-[2-ethyl-1-(1-ethylpropyl)-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;

1-{3-chloro-4-[1-(1-ethylpropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;

1-(dicyclopropylmethyl)-2-ethyl-4-(5-fluoro-4-methoxy-2-methylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(dicyclopropylmethyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(dicyclopropylmethyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(dicyclopropylmethyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-1-(dicyclopropylmethyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-1-(dicyclopropylmethyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(dicyclopropylmethyl)-2-ethyl-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(dicyclopropylmethyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-4-methoxyphenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methoxyphenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methoxyphenyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

1-(1-ethyl-3-methoxypropyl)-2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(4-methoxy-2,5-dimethylphenyl)-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-1H-imidazo[4,5-c]pyridine;

1-(1-ethyl-3-methoxypropyl)-4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methylphenyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methylphenl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(methylsulfonyl)phenyl]-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

1-{3-chloro-4-[1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;

1-{3-chloro-4-[2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridin-4-yl]phenyl}-1-ethanone;

1-{5-[1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridin-4-yl]-6-methyl-2-pyridinyl}-1-ethanone;

1-{5-[2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridin-4-yl]-6-methyl-2-pyridinyl}-1-ethanone;

1-(1-ethyl-3-methoxypropyl)-2-methoxy-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethoxy-3-pyridinyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethyl-3-pyridinyl)-1-(1-ethyl-3-methoxypropyl)-2-methoxy-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethyl-3-pyridinyl)-2-ethyl-1-(1-ethyl-3-methoxypropyl)-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-ethyl-3-methoxypropyl)-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

1-(1-ethyl-3-methoxypropyl)-2-methoxy-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2,4-dichlorophenyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(trifluoromethyl)phenyl]-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methylphenyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2-chloro-5-fluoro-4-methylphenyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

2-methoxy-4-(4-methoxy-2,5-dimethylphenyl)-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

2-ethyl-4-(4-methoxy-2,5-dimethylphenyl)-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

2-ethyl-4-(5-fluoro-4-methoxy-2-methylphenyl)-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(5-fluoro-4-methoxy-2-methylphenyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

2-methoxy-1-[1-(methoxymethyl)propyl]-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-[1-(methoxymethyl)propyl]-4-(6-methoxy-2-methyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethoxy-3-pyridinyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethoxy-3-pyridinyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethyl-3-pyridinyl)-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

4-(2,6-dimethyl-3-pyridinyl)-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

2-ethyl-1-(1-(methoxymethyl)propyl]-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

2-methoxy-1-[1-(methoxymethyl)propyl]-4-(2,5,6-trimethyl-3-pyridinyl)-1H-imidazo[4,5-c]pyridine;

4-[2-chloro-4-(methylsulfonyl)phenyl]-2-ethyl-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine; and

4-[2-chloro-4-(methylsulfonyl)phenyl]-2-methoxy-1-[1-(methoxymethyl)propyl]-1H-imidazo[4,5-c]pyridine;

or a pharmaceutically acceptable salt form thereof.

[3j] In another more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

R¹ is C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R¹ is also substituted with 0-3 substituents independently selected at each occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and —NR^(13a)R^(16a).

[3k] In another even more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group cyclopropyl, cyclobutyl, and cyclopentyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₄₋₈ cycloalkyl, wherein one carbon atom in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, NCOR^(14b)— and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and —NR^(13a)R^(16a);

R^(1a) is aryl and is selected from the group phenyl and indanyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-1 substituents selected from the group —CN, OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R³ and R⁷ are independently selected at each occurrence from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[3l] In another still more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted with 0-1 substituents selected from the group —CN, —CO₂R^(13a), and C₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₃, —OR^(13a), —OH, —OCH₃, —OCH₂CH₃, —CH₂OCH₃, —CH₂CH₂OCH₃, and —NR^(13a)R^(16a);

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁷ are independently selected at each occurrence from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[3m] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

R¹ is substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, and CF₃;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁷ are independently selected at each occurrence from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[3n] In another even further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

R¹ is substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH₂OCH₃, —CH₂CH₂OCH₃, F, and CF₃; and,

R^(1a) is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[3o] In another still further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[3p] In another still further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[3q] In another more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl, C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ alkoxy-C₁₋₄ alkyl;

R¹ is substituted with a C₃₋₈ cycloalkyl group, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl group is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—;

R¹ is also substituted with 0-3 substituents independently selected at each occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R¹⁹a, —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR^(17h), —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R^(1c) is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a), —OC(O)R^(14b), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b) and wherein any sulfur atom is optionally monooxidized or dioxidized.

[3r] In another even more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₈ cycloalkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl group, wherein 0-1 carbon atoms in the C₄₋₆ cycloalkyl group is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

R^(1a) is aryl and is selected from the group phenyl and indanyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-1 substituents selected from the group —CN, OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R³ and R⁷ are independently selected at each occurrence from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[3s] In another still more preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

X is selected from the group O, S and a bond;

R¹ is C₁₋₆ alkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₄ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, F, CF₃, —OR^(13a), —NR^(13a)R^(16a), —CH₂OCH₃, —CH₂CH₂OCH₃, and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ and R⁷ are independently selected at each occurrence from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[3t] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl, CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ and R⁷ are independently selected at each occurrence from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[3u] In another even further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[3v] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[3w] In another further preferred embodiment, the present invention provides a novel compound of formula Ib, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[4] In another preferred embodiment, the present invention provides a novel compound of formula Ic:

[4a] In another more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, and C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂-group;

R^(1a) is aryl and is selected from the group phenyl and indanyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-1 substituents selected from the group —CN, OH, Cl, F, and C₁₋₄ alkoxy;

R³ is selected from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[4b] In another even more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted C₁₋₆ alkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —CO₂R^(13a), and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a);

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂-group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂— and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ is selected from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —CO(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[4c] In another still more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

R¹ is substituted C₁;

R¹ is substituted with 0-1 substituents selected from the group —CN, —CO₂CH₃, and —CO₂CH₂CH₃;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl, CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

provided that R¹ is other than a —(CH₂)₁₋₄-aryl or —(CH₂)₁₋₄-heteroaryl wherein the aryl or heteroaryl group is substituted or unsubstituted;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ is selected from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[4d] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

R¹ is substituted (cyclopropyl)-C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 0-1 —CN;

R¹ is also substituted with 0-1 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCHCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[4e] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)-C₁ alkyl substituted with 1 substituent independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, Cl, F, and CF₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, and isoxazolyl, each heteroaryl being substituted on 0-2 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, OCH₃, C_(1,) F, and CF₃.

[4f] In an even further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

R¹ is selected from the group (cyclopropyl)CH—CH₃, (cyclopropyl)CH—CH₂CH₃, (cyclopropyl)CH—CH₂OCH₃, (cyclopropyl)CH—CH₂CH₂CH₃, (cyclopropyl)CH—CH₂CH₂OCH₃, (cyclopropyl)₂CH, phenyl(cyclopropyl)CH, furanyl(cyclopropyl)CH, thienyl(cyclopropyl)CH, isoxazolyl(cyclopropyl)CH, (CH₃-furanyl)(cyclopropyl)CH, (cyclobutyl)CH-CH₃, (cyclobutyl)CH—CH₂CH₃, (cyclobutyl)OH—OH₂OCH₃, (cyclobutyl)CH—CH₂CH₂CH₃, (cyclobutyl)CH—CH₂CH₂OCH₃, (cyclobutyl)₂CH, phenyl(cyclobutyl)CH, furanyl(cyclobutyl)CH, thienyl(cyclobutyl)CH, isoxazolyl(cyclobutyl)CH, and (CH₃-furanyl)(cyclobutyl)CH;

[4g] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[4h] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[4i] In another preferred embodiment, the present invention provides a novel compound of formula Ic, wherein the compound is selected from the group:

6-(2,4-bis(trifluoromethyl)phenyl-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-cyanophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxy-5-chlorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxy-5-methylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(2-hexyl)-9H-purine;

6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(3-heptyl)-9H-purine;

6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(3-hexyl)-9H-purine;

6-(2-chloro-4-methoxyphenyl)-8-ethyl-9-(4-heptyl)-9H-purine;

6-(2-chloro-4-methoxyphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxyphenyl)-9-(1-cyclopropylpropyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxyphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methoxyphenyl)-9-(dicyclopropylmethyl)-8-methoxy-9H-purine;

6-(2-chloro-4-methyl-5-fluorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methylphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2-chloro-4-methylphenyl)-8-ethyl-9-(4-heptyl)-9H-purine;

6-(2-chloro-4-methylphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;

6-(2-chloro-4-methylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethoxyphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2-chloro-4-trifluoromethoxyphenyl)-8-ethyl-9-(3-hexyl)-9H-purine;

6-(2-chloro-4-trifluoromethoxyphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethoxyphenyl)-9-(1-cyclopropylpropyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethoxyphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-hexyn-3-yl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-pentyn-3-yl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-pentyn-4-yl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(1-phenyl-2-butynyl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(2-heptyn-4-yl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)8-ethyl-9-(2-hexyn-4-yl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-(4-heptyl)-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-[(2-furanyl)-cyclopropylmethyl]-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-8-ethyl-9-[1-(2-furanyl)propyl]-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclobutylethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropyl-2-butynyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropyl-2-propenyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropylbutyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(1-cyclopropylpropyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-(dicyclopropylmethyl)-8-methoxy-9H-purine;

6-(2-chloro-4-trifluoromethylphenyl)-9-[1-cyclopropyl-1-(2-thienyl)methyl]-8-ethyl-9H-purine;

9-(1-cyclobutylethyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-[1-cyclopropyl-(3-methylisoxazol-5-yl)methyl]-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropyl-2-butynyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropyl-2-butynyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropyl-2-propenyl)-6-(2,4-dichloro-6-methylphenyl)-8-ethyl-9H-purine;

9-(1-cyclopropyl-2-propenyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropyl-2-propynyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

9(1-cyclopropyl-4′-fluorobenzyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylbenzyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylbenzyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

9-(1-cyclopropylbutyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2,4,6-trimethylphenyl)-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2-methyl-4-chlorophenyl)-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2-methyl-4-methoxyphenyl)-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

9-(1-cyclopropylbutyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

9-(1-cyclopropylethyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylethyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

9-(1-cyclopropylpentyl)-8-ethyl-6-(2-methyl-4-methoxyphenyl)-9H-purine;

9-(1-cyclopropylpropyl)-6-(2,4-dichloro-6-methylphenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylpropyl)-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine;

9-(1-cyclopropylpropyl)-8-ethyl-6-(2,4,6-trimethylphenyl)-9H-purine;

9-(1-cyclopropylpropyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

6-(2,4-dichloro-5-fluorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2,4-dichloro-6-methylphenyl)-8-ethyl-9-(2-penten-3-yl)-9H-purine;

6-(2,4-dichloro-6-methylphenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(1-hexyn-3-yl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(1-methoxycarbonylpropyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(1-phenyl-2-butynyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(2-heptyn-4-yl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(2-hexyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(2-hexyn-4-yl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(2-penten-3-yl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(3-heptyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(3-hexyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(3-pentyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-(4-heptyl)-9H-purine;

6-(2,4-dichlorophenyl)-8-ethyl-9-[1-(2-methylcyclopropyl)ethyl]-9H-purine;

6-(2,4-dichlorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2,4-dichlorophenyl)-9-(dicyclopropylmethyl)-8-ethyl-9H-purine;

6-(2,4-dichlorophenyl)-9-(dicyclopropylmethyl)-8-methoxy-9H-purine;

6-(2,4-dichlorophenyl)-9-(diphenylmethyl)-8-ethyl-9H-purine;

9-(dicyclopropylmethyl)-6-(2,4-dimethylphenyl)-8-ethyl-9H-purine;

9-(dicyclopropylmethyl)-6-(2,4-dimethylphenyl)-8-ethyl-9H-purine;

9-(dicyclopropylmethyl)-6-(2,6-dimethoxypyridin-3-yl)-8-methoxy-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2,4,5-trichlorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methoxy-4-trifluoromethylphenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-chlorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-dimethylaminophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-methoxy-5-chlorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-methoxy-5-fluorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-chloro-4-methoxy-5-fluorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-4-methoxyphenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

9-(dicyclopropylmethyl)-8-ethyl-6-(2-trifluoromethyl-4-propyloxyphenyl)-9H-purine;

6-(2,6-dimethoxypyridin-3-yl)-8-ethyl-9-(2-pentyl)-9H-purine;

6-(2,4-dimethylphenyl)-8-ethyl-9-(2-pentyl)-9H-purine;

8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9-(2-pentyl)-9H-purine;

8-ethyl-6-(2-methyl-4,5-dimethoxyphenyl)-9-(3-pentyl)-9H-purine;

8-ethyl-9-(1-hexen-3-yl)-6-(2-methyl-4,5-dimethoxyphenyl)-9H-purine;

8-ethyl-9-(1-hexen-3-yl)-6-(2-trifluoromethyl-4-3methoxyphenyl)-9H-purine;

8-ethyl-9-(2-hexyl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(2-pentyl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(3-hexyl)-6-(2-methyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(3-hexyl)-6-(2-trifluoromethyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(3-pentyl)-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

8-ethyl-9-(4-heptyl)-6-(2-methyl-4-chlorophenyl)-9H-purine;

8-ethyl-9-(4-heptyl)-6-(2-methyl-4-methoxyphenyl)-9H-purine;

8-ethyl-9-(4-heptyl)-6-(2-trifluoromethyl-4-chlorophenyl)-9H-purine;

8-ethyl-9-(4-heptyl)-6-(2-trifluoromethyl-4 methoxyphenyl)-9H-purine; and

9-(dicyclopropylmethyl)-8-ethyl-6-(2-methyl-6-methoxy-3-pyridyl)-9H-purine;

or a pharmaceutically acceptable salt form thereof.

[4j] In another more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

R¹ is C₃₋₈ cycloalkyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R¹ is also substituted with 0-3 substituents independently selected at each occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and —NR^(13a)R^(16a).

[4k] In another even more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group cyclopropyl, cyclobutyl, and cyclopentyl;

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), and C₄₋₈ cycloalkyl, wherein one carbon atom in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and —NR^(13a)R^(16a);

R^(1a) is aryl and is selected from the group phenyl and indanyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-1 substituents selected from the group —CN, OH, Cl , F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R³ is selected from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[4l] In another still more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

X is selected from the group O, S and a bond;

R¹ is substituted with 0-1 substituents selected from the group —CN, —CO₂R^(13a), and C₄₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR ^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₃, —OR^(13a), —OH, —OCH₃, —OCH₂CH₃, —CH₂OCH₃, —CH₂CH₂OCH₃, and NR^(13a)R^(16a);

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-3 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ is selected from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[4m] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

R¹ is substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂OH₂OCH₃, F, and CF₃;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ is selected from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[4n] In another even further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

R¹ is substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH₂OCH₃, —CH₂CH₂OCH₃, F, and CF₃; and,

R^(1a) is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[4o] In another still further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[4p] In another still further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[4q] In another more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl, C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ alkoxy-C₁₋₄ alkyl;

R¹ is substituted with a C₃₋₈ cycloalkyl group, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl group is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—;

R¹ is also substituted with 0-3 substituents independently selected at each occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); and,

R^(1c) is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR^(13a), SH, S(O)_(n)R^(14b), —COR^(13a), —OC(O)R^(14b), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b) and wherein any sulfur atom is optionally monooxidized or dioxidized.

[4r] In another even more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

X is selected from the group O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, and C₃₋₈ cycloalkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl group, wherein 0-1 carbon atoms in the C₄₋₆ cycloalkyl group is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, CF₃, CF₂CF₃, —OR^(13a), —NR^(13a)R^(16a), C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

R^(1a) is aryl and is selected from the group phenyl and indanyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, CF₃, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R² is selected from the group C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-1 substituents selected from the group —CN, OH, Cl, F, and C₁₋₄ alkoxy;

R⁹ is independently selected at each occurrence from the group H, C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R³ is selected from the group H, Br, Cl, F, —CN, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₁₋₄ alkoxy, NH₂, C₁₋₄ alkylamino, and (C₁₋₄ alkyl)₂-amino;

R¹³ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl-C₁₋₂ alkyl, aryl(C₁₋₂ alkyl)-, and heteroaryl(C₁₋₂ alkyl)-;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₂ haloalkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₂ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷, R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is phenyl substituted with 1-4 substituents independently selected at each occurrence from the group C₁₋₄ alkyl, C₃₋₆ cycloalkyl, —OR¹⁷, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —NR¹⁵COR¹⁷, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 1-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, C₁₋₄ haloalkyl, —CN, —OR¹⁷, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[4s] In another still more preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

X is selected from the group O, S and a bond;

R¹ is C₁₋₆ alkyl;

R¹ is substituted with a C₃₋₆ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₄ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, and —NR^(13a)—;

R¹ is also substituted with 0-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, F, CF₃, —OR^(13a), —NR^(13a)R^(16a), —CH₂OCH₃, —CH₂CH₂OCH₃, and C₃₋₆ cycloalkyl which is substituted with 0-1 CH₃ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than a cyclohexyl-(CH₂)₂— group;

R^(1a) is aryl and is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, OCH(CH₃)_(2, OCH) ₂CH₂CH₃, and OCF₃, and 0-3 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, and indazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

R³ is selected from the group H, CH₃, CH₂CH₃, CH(CH₃)₂, and CH₂CH₂CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, indolyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, and benzoxazolin-2-on-yl, each heteroaryl being substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃.

[4t] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂; —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, CH₃-cyclopropyl, cyclobutyl, CH₃-cyclobutyl, cyclopentyl, CH₃-cyclopentyl;

R^(1a) is phenyl substituted with 0-1 substituents selected from OCH₃, OCH₂CH₃, and OCF₃, and 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, and tetrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group CH₃, CO₂CH₃, COCH₃ and SO₂CH₃;

R² is selected from the group CH₃, CH₂CH₃, and CH(CH₃)₂;

R³ is selected from the group H and CH₃;

aryl is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂; and,

heteroaryl is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, SCH₃, SO₂CH₃, —NH₂, —NHCH₃, —N(CH₃)₂, —C(O)NH₂, —C(O)NHCH₃, and —C(O)N(CH₃)₂.

[4u] In another even further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

R¹ is (cyclopropyl)C₁ alkyl or (cyclobutyl)C₁ alkyl;

R¹ is substituted with 1-2 substituents independently selected at each occurrence from the group R^(1a), R^(1b), CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, —(CH₂)₃CH₃, —CH═CH₂, —CH═CH(CH₃), —CH≡CH, —CH≡C(CH₃), —CH₂OCH₃, —CH₂CH₂OCH₃, F, CF₃, cyclopropyl, and CH₃-cyclopropyl;

R^(1a) is phenyl substituted with 0-2 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, Br, Cl, F, CF₃, —CN, and SCH₃;

R^(1b) is heteroaryl and is selected from the group furanyl, thienyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, and pyrazolyl, each heteroaryl being substituted on 0-3 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, OCH₃, OCH₂CH₃, OCF₃, Br, Cl, F, CF₃, —CN, and SCH₃.

[4v] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

D is phenyl substituted with 2-4 substituents independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[4w] In another further preferred embodiment, the present invention provides a novel compound of formula Ic, wherein:

D is pyridyl substituted on 2-4 carbon atoms with a substituent independently selected at each occurrence from the group CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₃, cyclopropyl, OCH₃, OCH₂CH₃, OCH(CH₃)₂, OCH₂CH₂CH₃, OCF₃, Br, Cl, F, and CF₃.

[5] In a third embodiment, the present invention provides a novel pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of formula (I):

or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:

A is N or C—R⁷;

B is N or C—R⁸;

provided that at least one of the groups A and B is N;

D is an aryl or heteroaryl group attached through an unsaturated carbon atom;

X is selected from the group CH—R⁹, N—R¹⁰, O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl, C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, —SO₂—C₁₋₁₀ alkyl, —SO₂—R^(1a), and —SO₂—R^(1b);

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a), —NCO₂R^(14b), —NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R¹ is also substituted with 0-3 substituents independently selected at each occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), —NR^(13a)R^(16a), and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than:

(a) a 3-cyclopropyl-3-methoxypropyl group;

(b) an unsubstituted-(alkoxy)methyl group; and,

(c) a 1-hydroxyalkyl group;

also provided that when R¹ alkyl substituted with OH, then the carbon adjacent to the ring N is other than CH₂;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R^(1a) being substituted with 0-5 substituents independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R^(1c) is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a), —OC(O)

R^(14b), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b) and wherein any sulfur atom is optionally monooxidized or dioxidized;

R² is selected from the group C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-3 substituents selected from the group —CN, hydroxy, halo and C₁₋₄ alkoxy;

alternatively R², in the case where X is a bond, is selected from the group —CN, CF₃ and C₂F₅;

R³, R⁷ and R⁸ are independently selected at each occurrence from the group H, Br, Cl, F, I, —CN, C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, C₁₋₄ alkylsulfinyl, C₁₋₄ alkylsulfonyl, amino, C₁₋₄ alkylamino, (C₁₋₄ alkyl)₂amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group C₁₋₇ alkyl, C₃₋₈ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, C₁₋₄ alkylthio, C₁₋₄ alkyl sulfinyl, C₁₋₄ alkylsulfonyl, C₁₋₆ alkylamino and C₁₋₄ alkyl)₂amino;

provided that when R¹ is unsubstituted C₁₋₁₀ alkyl, then R³ is other than substituted or unsubstituted phenyl;

R⁹ and R¹⁰ are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl-C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl, aryl(C₁₋₄ alkyl)-, heteroaryl and heteroaryl (C₁₋₄ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl, aryl(C₁₋₄ alkyl)-, heteroaryl and heteroaryl(C₁₋₄ alkyl)- and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy C₁₋₄ haloalkoxy, and dimethylamino;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(14b) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷ is selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, cycloalkyl-C₃₋₆ alkyl, C₁₋₂ alkoy-C₁₋₂ alkyl, C₁₋₄ haloalkyl, R¹⁴S(O)_(n)C₁₋₄ alkyl, and R^(17b)R^(19b)N—C₂₋₄ alkyl;

R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

alternatively, in an NR^(17b)R^(19b) moiety, R^(17b) and R^(19b) taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is independently selected at each occurrence from the group phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, methylenedioxy, C₁₋₄ alkoxy-C₁₋₄ alkoxy, —OR¹⁷, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, —NO₂, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and up to 1 phenyl, each phenyl substituent being substituted with 0-4 substituents selected from the group C₁₋₃ alkyl, C₁₋₃ alkoxy, Br, Cl, F, I, —CN, dimethylamino, CF₃, C₂F₅, OCF₃, SO₂Me and acetyl; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

[6] In a second embodiment, the present invention provides a novel method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals, comprising: administering to the mammal a therapeutically effective amount of a compound of formula (I):

or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:

A is N or C—R⁷;

B is N or C—R⁸; provided that at least one of the groups A and B is N;

D is an aryl or heteroaryl group attached through an unsaturated carbon atom;

X is selected from the group CH—R⁹, N—R¹⁰, O, S(O)_(n) and a bond;

n is 0, 1 or 2;

R¹ is selected from the group C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl, C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, —SO₂—C₁₋₁₀ alkyl, —SO₂—R^(1a), and —SO₂—R^(1b);

R¹ is substituted with 0-1 substituents selected from the group —CN, —S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R¹ is also substituted with 0-3 substituents independently selected at each occurrence from the group R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), —NR^(13a)R^(16a), and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—;

provided that R¹ is other than:

(a) a 3-cyclopropyl-3-methoxypropyl group;

(b) an unsubstituted-(alkoxy)methyl group; and,

(c) a 1-hydroxyalkyl group;

also provided that when R¹ alkyl substituted with OH, then the carbon adjacent to the ring N is other than CH₂;

R^(1a) is aryl and is selected from the group phenyl, naphthyl, indanyl and indenyl, each R^(1a) being substituted with 0-5 substituents independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a);

R^(1b) is heteroaryl and is selected from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b);

R^(1c) is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR^(13a), SH, S(O)_(n)R^(14b), —COR^(13a), —OC(O) R^(14b), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b) and wherein any sulfur atom is optionally monooxidized or dioxidized;

R² is selected from the group C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-3 substituents selected from the group —CN, hydroxy, halo and C₁₋₄ alkoxy;

alternatively R², in the case where X is a bond, is selected from the group —CN, CF₃ and C₂F₅;

R³, R⁷ and R⁸ are independently selected at each occurrence from the group H, Br, Cl, F, I, —CN, C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, C₁₋₄ alkylsulfinyl, C₁₋₄ alkylsulfonyl, amino, C₁₋₄ alkylamino, (C₁₋₄ alkyl)₂amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group C₁₋₇ alkyl, C₃₋₈ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, C₁₋₄ alkylthio, C₁₋₄ alkyl sulfinyl, C₁₋₄ alkylsulfonyl, C₁₋₆ alkylamino and (C₁₋₄ alkyl)₂amino;

provided that when R¹ is unsubstituted C₁₋₁₀ alkyl, then R³ is other than substituted or unsubstituted phenyl;

R⁹ and R¹⁰ are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl-C₁₋₄ alkyl and C₃₋₈ cycloalkyl;

R¹³ is selected from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl, aryl(C₁₋₄ alkyl)-, heteroaryl and heteroaryl(C₁₋₄ alkyl)-;

R^(13a) and R^(16a) are independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁴ is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl, aryl(C₁₋₄ alkyl)-, heteroaryl and heteroaryl(C₁₋₄ alkyl)- and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy C₁₋₄ haloalkoxy, and dimethylamino;

R^(14a) is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(14b)is selected from the group C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁵ is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino;

R^(15a) is independently selected at each occurrence from the group H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl;

R¹⁷ is selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₁₋₄ haloalkyl, R¹⁴S(O)_(n)—C₁₋₄ alkyl, and R^(17b)R^(19b)N—C₂₋₄ alkyl;

R¹⁸ and R¹⁹ are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkoyl, and C₁₋₄ haloalkyl;

alternatively, in an NR¹⁹R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴;

alternatively, in an NR^(17b)R^(19b) moiety, R^(17b) and R^(19b) taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperaziinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group R¹³, CO₂R¹⁴, CR¹⁴ and SOR¹⁴;

R^(17a) and R^(19a) are independently selected at each occurrence from the group H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl;

aryl is independently selected at each occurrence from the group phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, methylenedioxy, C₁₋₄ alkoxy-C₁₋₄ alkoxy, —OR¹⁷, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, —NO₂, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and up to 1 phenyl, each phenyl substituent being substituted with 0-4 substituents selected from the group C₁₋₃ alkyl, C₁₋₃ alkoxy, Br, Cl, F, I, —CN, dimethylamino, CF₃, C₂F₅, OCF₃, SO₂Me and acetyl; and,

heteroaryl is independently selected at each occurrence from the group pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(m)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a).

In another preferred embodiment, R¹ is other than a cyclohexyl-(CH₂)_(1, 2, 3, 4, 5, 6, 7, 8, 9, or 10)— group.

In another preferred embodiment, R¹ is other than an aryl-(CH₂)_(1, 2, 3, 4, 5, 6, 7, 8, 9, or 10)— group, wherein the aryl group is substituted or unsubstituted.

In another preferred embodiment, R¹ is other than a heteroaryl-(CH₂)_(1, 2, 3, 4, 5, 6, 7, 8, 9, or 10)— group, wherein the heteroaryl group is substituted or unsubstituted.

In another preferred embodiment, R¹ is other than a heterocyclyl-(CH₂)_(1, 2, 3, 4, 5, 6, 7, 8, 9, or 10)— group, wherein the heterocyclyl group is substituted or unsubstituted.

In another preferred embodiment, when D is imidazole or triazole, R¹ is other than unsubstituted C_(1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) linear or branched alkyl or C_(3, 4, 5, 6, 7, or 8) cycloalkyl.

In another preferred embodiment, R^(1a) is not substituted with OR¹⁷.

Many compounds of this invention have one or more asymmetric centers or planes. Unless otherwise indicated, all chiral (enantiomeric and diastereomeric) and racemic forms are included in the present invention. Many geometric isomers of olefins, C═N double bonds, and the like can also be present in the compounds, and all such stable isomers are contemplated in the present invention. The compounds may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. All chiral, (enantiomeric and diastereomeric) and racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomer form is specifically indicated.

The term “alkyl” includes both branched and straight-chain alkyl having the specified number of carbon atoms. “Alkenyl” includes hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon-carbon bonds which may occur in any stable point along the chain, such as ethenyl, propenyl, and the like. “Alkynyl” includes hydrocarbon chains of either a straight or branched configuration and one or more triple carbon-carbon bonds which may occur in any stable point along the chain, such as ethynyl, propynyl and the like. “Haloalkyl” is intended to include both branched and straight-chain alkyl having the specified number of carbon atoms, substituted with 1 or more halogen; “alkoxy” represents an alkyl group of indicated number of carbon atoms attached through an oxygen bridge; “cycloalkyl” is intended to include saturated ring groups, including mono-,bi- or poly-cyclic ring systems, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and so forth. “Halo” or “halogen” includes fluoro, chloro, bromo, and iodo.

The term “substituted”, as used herein, means that one or more hydrogen on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto (i.e., ═O), then 2 hydrogens on the atom are replaced.

Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. By “stable compound” or “stable structure” is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

The term “pharmaceutically acceptable salts” includes acid or base salts of the compounds of formulas (I) and (II). Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like.

Pharmaceutically acceptable salts of the compounds of the invention can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, the disclosure of which is hereby incorporated by reference.

“Prodrugs” are considered to be any covalently bonded carriers which release the active parent drug of formula (I) or (II) in vivo when such prodrug is administered to a mammalian subject. Prodrugs of the compounds of formula (I) and (II) are prepared by modifying functional groups present in the compounds in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compounds. Prodrugs include compounds wherein hydroxy, amine, or sulfhydryl groups are bonded to any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl, amino, or sulfhydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol and amine functional groups in the compounds of formulas (I) and (II); and the like.

The term “therapeutically effective amount” of a compound of this invention means an amount effective to antagonize abnormal level of CRF or treat the symptoms of affective disorder, anxiety, depression, immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in a host.

Synthesis

Compounds of formula (I) can be prepared by the following synthetic routes and schemes. Where a detailed description is not provided, it is assumed that those skilled in the art of organic synthesis will readily understand the meaning.

Synthesis of compounds of formula (I) may be prepared by the reaction shown in Scheme 1.

A compound of formula (II) can be alkylated on the imidazole nitrogen atom with an appropriate reagent. Typical conditions for this transformation include treatment of compound (II) with a base, such as sodium hydride, potassium tert-butoxide, sodium hexamethyldisilazide, etc., followed by a reagent J—R¹, where J represents a halide (chloride, bromide or iodide) or psuedohalide (tosylate, mesylate, triflate, etc.), at an appropriate temperature (0° C. or room temperature, with warming if necessary) in a solvent such as tetrahydrofuran, dimethylformamide or dimethylsulfoxide. Alternatively, this reaction may be performed using the Mitsunobu conditions (Mitsunobu, Synthesis 1981, pp. 1-28). The compound (II) is treated with an alcohol compound R¹OH, along with a phosphine (triphenyl, tributyl, etc.) and a phosphine-activating reagent such as diethyl azodicarboxylate.

Compounds of Formula (II) may be prepared according to the route shown in Scheme 2.

A compound of Formula (III) may be coupled to an aromatic compound of Formula (IV), with elimination of the elements of M—K. For compound (III), K represents a halide, psuedohalide (such as mesylate, tosylate or triflate), or thiomethyl, and P represents a protecting group (if the conditions of the reaction warrant protection of the imidazole N—H; otherwise, P can be H). Suitable P groups may include benzyl, 4-methoxybenzyl, methoxymethyl, trimethylsilylethoxymethyl, tert-butoxycarbonyl or benzyloxycarbonyl. For compound (IV), M represents groups such as lithium, bromomagnesium, chlorozinc, (dihydroxy)boron, (dialkoxy)boron, trialkylstannyl and the like. The coupling reaction may be performed in the presence of an appropriate catalyst, such as tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride, [1,3-bis(diphenylphosphino)propane]nickel dichloride, etc. Two particularly useful methods involve the coupling of chloroheterocycles with in-situ-prepared arylzinc reagents according to the method of Negishi et al. (J. Org. Chem. 1977, 42, 1821), and the coupling with arylboronic esters according to the method of Suzuki et al. (Chem. Letters 1989, 1405). Appropriate solvents for reactions of this type usually include tetrahydrofuran, diethyl ether, dimethylformamide, or dimethylsulfoxide. Typical temperatures range from ambient up to the boiling point of the solvent. Once coupled, the P group may be removed to afford compound (II). Conditions for the removal of the protecting groups are well known to those familiar to the art of organic synthesis; e.g. hydrogenation to remove benzyl or benzyloxycarbonyl, a fluoride source (such as tetrabutylammonium fluoride) to remove silylethoxymethyl, an acid source (such as trifluoroacetic acid) to remove tert-butoxycarbonyl or 4-methoxybenzyl, etc.

Compounds of formula (III) can be prepared according to the plan shown in Scheme 3.

A diamine compound of formula (V) (in this case, P is a group such as benzyl, which can be introduced already attached to the nitrogen atom; otherwise, P could represent H initially, and another protecting group being introduced in a later step) is used in a cyclocondensation reaction to make the imidazole ring. The conditions used will, of course, depend on the X group chosen, and may include the intermediacy of the compound (VI). A review of imidazole-forming reactions may be found in Comprehensive Heterocyclic Chemistry (Pergamon Press, 1984) vol. 5, pp. 457-498.

Preparation of compounds of formula (V) wherein both A and B are nitrogen atoms may proceed according to the route of Scheme 4.

A compound of formula (VII) may be available from commercial sources, particularly for K=chloride. Compounds bearing psuedohalide K groups may be available from the corresponding dihydroxy compounds by treatment with an appropriate activating reagent, such as an organosulfonic anhydride or sulfonyl chloride. Compound (VII) may be converted to (V) by either (i) monoalkylation with a compound P—NH₂, followed by reduction of the nitro group; (ii) reduction of the nitro group, to give an amine compound of formula (VIII), followed by monoalkylation with a compound P—NH₂; or (iii) use of a source of ammonia (ammonia gas, ammonium hydroxide, etc.) in either route, followed by protection of the amine group with the group P. Pyrimidine chemistry of this type is well represented in the literature, and is reviewed in Comprehensive Heterocyclic Chemistry, vol. 6. Alkylation of chloropyrimidines with amine compounds can be accomplished under either acidic (e.g. HCl or acetic) or basic (trialkylamines, potassium tert-butoxide, etc.) conditions. Nitro groups in compounds of this type can be reduced to amino groups using one of any number of conditions, including catalytic hydrogenation, tin dichloride, sodium dithionite, zinc metal, iron powder, etc.

Preparation of compounds of formula (V) wherein either A or B represent nitrogen atoms is shown in Scheme 5.

An hydroxypyridone compound of formula (IX) can be nitrated to give compound (X) employing conditions such as concentrated or fuming nitric acid, optionally in the presence of concentrated sulfuric or acetic acid. The hydroxypyridone can be selectively monoactivated with a K group to give a compound of formula (XI); one method to do this involves treatment of the dicyclohexylamine salt of compound (X) with phosphorus oxychloride to give (XI) wherein K═Cl. Alternatively, both the hydroxy and pyridone groups in compound (X) can be activated at the same time, using stronger conditions such as phosphorus oxychloride and heat, or excess toluenesulfonic anhydride, to give compound (XII). Compound (XI) may be converted to the protected amine compound (XIII) using the same general route discussed above for the pyrimidines. Selective monoalkylation using compound (XII) is also possible, but will probably give mixtures of regioisomeric products (XIV) and (XV). The nitro groups in these compounds can then be reduced as discussed above, to give compounds for formula (V) wherein either A or B is nitrogen.

An alternative approach to the method involving introduction of the R¹ group at the initial step is shown in Scheme 6.

This is particularly useful in the cases where R¹ represents a group where alkylation of compound (II) is impractical (e.g. a very bulky R¹ group), but can also be used in a general manner. Here, compounds of formula (XVI) or (XVII) (either amino- or nitro-pyridines or pyrimidines) are alkylated with an amine reagent R¹—NH₂, under either acidic or basic conditions as described above. Nitro compound (XVIII) can be converted to amine compound (XIX) by nitro reduction reactions described earlier. Compound (XIX) can be cyclized to imidazole compound (XX). As above, this reaction will depend upon the choice of X group. For example, for X═CHR⁹, one can use an orthoester reagent such as R²CH(R⁹)C(OR)₃, with heating in neat solution or high-boiling solvents, and the optional presence of an acid catalyst (such as hydrochloric or sulfuric acid) (see Montgomery and Temple, J. Org. Chem. 1960, 25, 395). For X═NR¹⁰, the cyclization is performed using reagents such as an guanidine reagent of the structure R²R¹⁰N—C(═NH)NH₂ or a urea-derived reagent of the structure R²R¹⁰N—C(═NH)D, where D represents a group like OCH₃, SCH₃ or SO₂CH₃. For X═O, the ring is formed using a reagent of the structure (R²O)₄C (with acetic acid catalysis), provided one has access to the reagent with the R² group of choice (see Brown and Lynn, J. Chem. Soc. Perkin Trans. I 1974, 349). Alternatively, the diamine (XIX) is treated with phosgene, followed by O-alkylation to introduce the R² group (such as a reagent like R²—I or R²—Br). A similar route can be used for X═S, which would use thiophosgene or some similar reagent, followed by S-alkylation with the R² group. The sulfur atom in this compound (and sulfide groups throughout the molecule in general) can be oxidized to either the sulfoxide or sulfone if desired by treatment with an appropriate oxidizing agent such as potassium permanganate, potassium peroxomonosulfate or m-chloroperbenzoic acid. Finally, compound (XX) can be used in an aryl coupling reaction as described above to replace the K group with the desired aryl group in compound (I). Methods of synthesis of compounds R¹—OH, R¹—J and R¹—NH₂ are related, in that the alcohol can be used in the synthesis of the other two compounds, as is shown in Scheme 7.

For example, the hydroxy group may be converted to the following J groups, using the indicated reagents (this route is not limited to these J groups): methanesulfonate, using methanesulfonyl chloride or anhydride and an appropriate base; toluenesulfonate, using toluenesulfonyl chloride or anhydride and an appropriate base; iodide; using iodine/triphenylphosphine; bromide, using phosphorus tribromide or carbon tetrabromide/triphenylphosphine; or trifluoromethanesulfonate, using trifluoromethane-sulfonic anhydride and an appropriate base. Both compounds R¹—OH and R¹—J are used in the methods portrayed in Scheme 1. Conversion of R¹—J to R¹—N₃ requires the use of an azide source, such as sodium azide, and a solvent such as dimethylsulfoxide or dimethylformamide, or water and a phase-transfer catalyst (such as tetrabutylammonium hydrogen sulfate). Reduction of the azide compound R¹—N₃ to R¹—NH₂ may be accomplished using reagents such as sodium borohydride or triphenylphosphine, or hydrogen gas and a catalyst (such as palladium on carbon). The amine R¹—NH₂ may then be employed in the methods portrayed in Scheme 6.

In the cases where the compound R¹—OH could be represented by a structure of formula (XXI) (Scheme 8), wherein R^(1a) and R^(1b) represents substructures which, taken together with the carbinol methine group, comprise the entire group R¹, this compound may be prepared by addition to a carbonyl compound.

This route is particularly useful in the case where R^(1a) or R^(1b) represents a cycloalkyl group, such as cyclopropyl. An organometallic reagent (where M′ represents a metallic group, such as Li, CUCN, CuI, MgCl, MgBr, MgI, ZnCl, CrCl, etc.) can be allowed to react with an aldehyde reagent to prepare the alcohol compound of formula (XXI). Alternatively, a ketone of formula (XXII) may be treated with a reducing agent, such as sodium borohydride, lithium aluminum hydride, etc., which will also generate the alcohol of formula (XXI). Standard methods of ketone synthesis may be used where appropriate in the preparation of compounds for formula (XXII), which will be familiar to those skilled in the art of organic synthesis.

An homologous approach may also be employed in the synthesis of alcohols R¹—OH, involving the ring-opening reaction of cyclic ether compounds with organometallic reagents (Scheme 9).

Here, an organometallic reagent R^(1a)—M″ is used, where M″ represents metals such as Mg, Zn or Cu. Especially useful is the method described in Huynh, et al., Tetrahedron Letters 1979, (17), pp. 1503-1506, where organomagnesium reagents are allowed to react with cyclic ethers with catalysis provided by copper (I) iodide. Use of an epoxide compound of formula (XXIII) in this manner would result in synthesis of an alcohol compound of formula (XXIV), and use of an oxetane compound of formula (XXV) would generate an alcohol of formula (XXVI). Both compounds (XXIV) and (XXVI) are variants of R¹—OH.

Synthesis of compound R¹—NH₂ with formula (XXVII) is portrayed in Scheme 10.

A simple reductive amination of ketone (XXII) will produce amine (XXVII). This reaction may be performed using anhydrous ammonia in the presence of hydrogen and a catalyst. Alternatively, addition of an organometallic reagent to a nitrile compound gives and imine, which may be treated in situ with a reducing agent (such as sodium cyanoborohydride) to give amine (XXVII). Finally, a compound of formula (XXVIII), wherein Q is an optionally-substituted oxygen atom (i.e. an oxime) or nitrogen atom (i.e. a hydrazone), may be allowed to react with an organometallic reagent R^(1b)—M′″. Here, metallic groups M′″ such as MgBr, CuCl or CeCl₂ have been used in additions to oximes or hydrazones. The intermediate addition products of formula (XXIX) may be subjected to reductive cleavage (using conditions such as sodium/liquid ammonia or catalytic hydrogenation), which will afford amines (XXVII).

Amino acids, either naturally-occurring or synthetic, are potential sources of useful starting materials for the synthesis of the compounds of this invention. Scheme 11 shows some possible applications of this approach.

Protected amino acids of formula (XXXI) are prepared from the parent compounds of formula (XXX); useful protecting groups (“Prot”) include tert-butoxycarbonyl, benzyloxycarbonyl and triphenylmethyl. Standard texts in peptide chemistry describe this protection. The carboxylic acid group may be reduced using reagents such as lithium borohydride, which gives alcohol (XXXII). The hydroxy group may be converted to a leaving group “J” as described before. The compound of formula (XXXIII) may be treated with appropriate reagents to produce a wide variety of functional groups included in the scope of this invention (compound (XXXIV)); displacement of J with cyanide (sodium cyanide in warm dimethylformamide may be used here) gives a nitrile, displacement of J with a mercaptan (in the presence of a base, such as potassium carbonate) gives a disulfide, displacement of J with a secondary amine gives a tertiary amine, etc.

The compounds of Formula (I) with unsaturated R¹ groups can be a further source of compounds covered under this invention. Unsaturated (double and triple) bonds can take part in cycloaddition chemistry with appropriate reagents (Scheme 12). Cycloaddition of an alkyne compound of Formula XXXVI with 1,3-dienes to give six-membered ring compounds like that of Formula XXXVII (commonly known as the Diels-Alder reaction), and cycloaddition with 3-atom dipolar reagents to give heterocyclic compounds of Formula XXXVIII, are familiar to those skilled in the art of organic synthesis. One specific example of this approach is the synthesis of an isoxazole compounds of Formula XXXIX from the alkyne XXXVI and a nitrile oxide reagent.

The synthetic procedure in Scheme 13 shown below may be used to prepare 4,5-c imidazopyridines.

Nitration of 2,4-dihydroxypyridine (XXXX) with HNO₃ as described earlier (Koagel et al. Recl. Trav. Chim. Pays-Bas. 29, 38, 67, 1948) gave the corresponding 3-nitropyridone (XXXXI) which was treated with an organic amine base, such as cycloheptyl amine to give selectively the corresponding 4-chloropyridone (XXXXIII). This in turn was reacted with a primary amine RNH₂, where R is a group described earlier in an aprotic or protic solvent, such as CH₃CN, DMSO, DMF, or an alkyl alcohol in the presence of an organic or inorganic base, such as a trialkylamine, K₂CO₃, Na₂CO₃ etc, and in temperature range of 20-200° C. to give the 4-amino adduct (XXXXIII). Pyridone (XXXXIII) was converted to the 2-chloropyridine (XXXXIV) by treatment with POCl₃, and (XXXXIV) was coupled with an arylboronic acid ArB(OH)₂ under palladium catalysis to give (XXXXV). Nitropyridine (XXXXV) was reduced to the corresponding aminopyridine by use of Na₂S₂O₄ or a Fe, Sn or SnCl₂ and converted to the imidazo[4,5-c]pyridine in refluxing propionic acid. The same transformation can be affected by the use of a nitrile, an imidate, thioimidate or trialkylorthopropionate.

The synthetic procedure in Scheme 14 shown below may be used to prepare 4,5-b imidazopyridines.

Reaction of 4-chloropyridone (XXXXII) with an aryl halide, such as benzyl bromide in benzene and in the presence of Ag₂CO₃ as described in Scheme 13 (Smith A. M.; et al. J. Med. Chem. 36, 8, 1993) and at temperature ranges of 30-80° C. afforded the corresponding 2-benzyloxypyridine (XXXXVII). This was coupled with an arylboronic acid, ArB(OH)₂ under palladium-catalyzed conditions to give (XXXXIX). The benzyloxy group can be removed by treatment with a strong acid, such as trifluoroacetic, triflic, sulfuric, HCl, etc. to give pyridone (L). This was converted to the 2-halopyridine with the action of POX₃, PX₅ or the corresponding triflate, tosylate or mesylate, which was displaced with a primary amine RNH₂ to give (LI). The nitro group was reduced under conditions described in scheme 13 and the aminopyridine was cyclized to the imidazolo[4,5-b]pyridine (LII) under conditions described in scheme 13.

The following examples are provided to describe the invention in further detail. These examples, which set forth the best mode presently contemplated for carrying out the invention, are intended to illustrate and not to limit the invention.

The methods discussed below in the preparation of 8-ethyl-9-(1-ethylpentyl)-6-(2,4,6-trimethylphenyl)purine (Table 1, Example 2, Structure A) and 9-butyl-8-ethyl-6-(2,4,6-trimethylphenyl)purine (Table 1, Example 27, Structure A) may be used to prepare all of the examples of Structure A contained in Table 1, Table 1A and Table 1B, with minor procedural modifications where necessary and use of reagents of the appropriate structure.

The methods discussed below in the preparation of 3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-ethyl-3H-imidazol[4,5-b]pyridine (Table 1, Example 38, Structure B) and 1-(1-cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-ethyl-1H-imidazo[4,5-c]pyridine (Table 1, Example 38, Structure C) may be used to prepare many of the examples of Structures B and C contained in Table 1, Table 1A, Table 1B and Table 1C, with minor procedural modifications where necessary and use of reagents of the appropriate structure.

EXAMPLE 2 Preparation of 8-Ethyl-9-(1-ethylpentyl)-6-(2,4,6-trimethylphenyl)purine

Part A. A solution of 5-amino-4,6-dichloropyrimidine (10.0 g, 61.0 mmol) and triethylamine (12.8 mL, 91.5 mmol) in ethanol (100 mL) was treated with benzylamine (7.30 mL, 67.1 mmol), and heated to 50° C. overnight. The resulting mixture was cooled, and the resulting crystalline solid was collected by filtration. The solid was triturated with hexane, refiltered and dried under vacuum. A second crop was collected from the mother liquor and purified like the first crop to afford in total 12.67 g (48.8 mmol, 80%) of 5-amino-6-benzylamino-4-chloropyrimidine. TLC R_(F) 0.10 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.62 (1H, s), 7.13-6.97 (5H, m), 6.61 (1H, br t, J=5 Hz), 4.43 (2H, d, J=5.5 Hz), 4.24 (2H, br s). MS (NH₃-CI): m/e 238 (4), 237 (33), 236 (15), 235 (100).

Part B. A solution of the diamine from Part A (10.45 g, 44.5 mmol) and 3 drops concentrated hydrochloric acid in triethyl orthopropionate (70 mL) was heated to 100° C. for 1 hour, then cooled, poured into water (200 mL) and extracted with ethyl acetate (2×200 mL). The extracts were washed in sequence with brine (100 mL), then combined, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was separated by column chromatography (silica gel, 20:80 ethyl acetate-hexane) to afford the product, N-(6-benzylamino-4-chloropyrimidin-5-yl)-O-ethyl-propionimidate (12.82 g, 40.2 mmol, 90%) as a crystalline solid, m.p. 85-86° C. TLC R_(F) 0.25 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.19 (1H, s), 7.35-7.29 (5H, m), 5.21 (1H, br t, J=5 Hz), 4.70 (2H, d, J=5.9 Hz), 4.29 (2H, br), 2.15 (2H, br q, J=7.3 Hz), 1.35 (3H, t, J=7.0 Hz), 1.06 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e 322 (6), 321 (34), 320 (20), 319 (100).

Part C. A solution of the imidate compound prepared in Part B above (10.66 g, 33.4 mmol) and p-toluenesulfonic acid monohydrate (100 mg) in diphenyl ether (10 mL) was heated to 170° C. for 2 hours. The resulting mixture was cooled and poured into 50 mL water. This was extracted with ethyl acetate (2×50 mL), and the extracts were washed in sequence with brine (50 mL), combined, dried over anhydrous sodium sulfate, filtered and evaporated. The residual material was separated by column chromatography (silica gel, hexane to remove diphenyl ether, then 30:70 ethyl acetate-hexane) to afford the product, 9-benzyl-6-chloro-8-ethylpurine, as an oil (8.16 g, 29.9 mmol, 89%). TLC R_(F) 0.20 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.72 (1H, s), 7.37-7.29 (3H, m), 7.19-7.14 (2H, m), 5.46 (2H, s), 2.89 (2H, q, J=7.7 Hz), 1.38 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e 276 (6), 275 (36), 274 (20), 273 (100).

Part D. A solution of zinc chloride (5.32 g, 39.1 mmol) in anhydrous, freshly-distilled tetrahydrofuran (50 mL) was treated at ambient temperature with a solution of mesitylmagnesium bromide (39.1 mL, 1.0 M, 39.1 mmol) in diethyl ether. After 45 minutes, a separate flask containing a solution of bis(triphenylphosphine)-palladium dichloride (0.92 g, 1.3 mmol) in tetrahydrofuran (30 mL) was treated with a solution of diisobutylaluminum hydride (2.6 mL, 1.0 M, 2.6 mmol) in hexane. This mixture was allowed to stir for 15 minutes, then treated with the mesitylzinc chloride solution dropwise by cannula. Then, the chloropurine compound in 10 mL tetrahydrofuran solution was added by syringe, and the mixture was allowed to stir for 12 hours at ambient temperature. It was poured into water (150 mL), and acidified with dropwise addition of 1 N aqueous hydrochloric acid until the mixture is homogeneous. This is extracted with ethyl acetate (2×150 mL), and the extracts were washed in sequence with saturated brine solution (100 mL), combined, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was separated by column chromatography (silica gel, 30:70 ethyl acetate-hexane) to afford the product, 9-benzyl-8-ethyl-6-(2,4,6-trimethylphenyl)purine (6.68 g, 18.7 mmol, 72%), as an off-white waxy solid, m.p. 121-122° C. ¹H NMR (300 MHz, CDCl₃): d 9.00 (1H, s), 7.38-7.31 (3H, m), 7.23-7.21 (2H, m), 6.96 (2H, s), 5.50 (2H, s), 2.84 (2H, q, J=7.6 Hz), 2.33 (3H, s), 2.06 (6H, s), 1.26 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 359 (3), 358 (26), 357 (100).

Part E. A solution of the benzyl compound from Part D above (5.33 g, 14.95 mmol) in trifluoroacetic acid (320 mL) partitioned into four Parr bottles, and each was treated with 0.8 g 20% palladium hydroxide on carbon. The bottles were each subjected to hydrogenation (50 psi) in shaker apparati for 18 hours. The atmospheres were purged with nitrogen, and the solutions were combined, filtered through celite and evaporated. The residual material was separated by column chromatography (silica gel, 50:50 ethyl acetate-hexane) to afford the product, 8-ethyl-6-(2,4,6-trimethylphenyl)purine (3.75 g, 14.1 mmol, 94%), as a white crystalline solid, m.p. 215-217° C. TLC R_(F) 0.17 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 12.35 (1H, br s), 9.03 (1H, s), 6.96 (2H, s), 3.05 (2H, q, J=7.7 Hz), 2.32 (3H, s), 2.05 (6H, s), 1.50 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e 269 (2), 268 (19), 267 (100).

Part F. A solution of the purine compound from Part E above (200 mg, 0.75 mmol), 3-heptanol (0.13 mL, 0.90 mmol) and triphenylphosphine (0.24 g, 0.90 mmol) in freshly-distilled tetrahydrofuran (5 mL) was cooled to 0° C., and treated with diethyl azodicarboxylate (0.14 mL, 0.90 mmol) dropwise by syringe. The mixture was allowed to stir for 12 hours, then evaporated. The residual material was separated by column chromatography (silica gel, 15:85 ethyl acetate-hexane) to afford the title product as a white solid (0.152 g, 0.42 mmol, 56%), m.p. 99-100° C. TLC R_(F) 0.17 (10:90 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.91 (1H, s), 6.95 (2H, s), 4.22 (1H, br), 2.92 (2H, q, J=7.7 Hz), 2.41 (2H, br), 2.32 (3H, s), 2.10-1.98 (2H, m), 2.05 (3H, s), 2.04 (3H, s), 1.37 (3H, t, J=7.5 Hz), 1.34-1.23 (4H, m), 0.84 (3H, t, J=7.1 Hz), 0.81 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 367 (3), 366 (27), 365 (100).

EXAMPLE 27 Preparation of 9-Butyl-8-ethyl-6-(2,4,6-trimethylphenyl)purine

A solution of 8-ethyl-6-(2,4,6-trimethylphenyl)purine (200 mg, 0.75 mmol) in anhydrous dimethylfomamide (5 mL) was cooled to 0° C., and treated with sodium hydride dispersion in mineral oil (72 mg 50% w/w, 1.50 mmol). After 1 hour, bromobutane (0.10 mL, 0.90 mmol) was added by syringe, and the mixture was allowed to stir for 12 hours. It was poured into ethyl acetate (120 mL), and was washed with water (3×120 mL) and brine (100 mL). The aqueous layers were back-extracted in sequence with ethyl acetate (120 mL), and the extracts were combined, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was separated by column chromatography (silica gel, 20:80 ethyl acetate-hexane) to afford the title product as a viscous oil (64.2 mg, 0.20 mmol, 27%). TLC R_(F) 0.20 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.96 (1H, s), 6.95 (2H, s), 4.25 (2H, t, J=7.5 Hz), 2.93 (2H, q, J=7.7 Hz), 2.32 (3H, s), 2.04 (6H, s), 1.91-1.86 (2H, m), 1.50-1.38 (2H, m), 1.39 (3H, t, J=7.7 Hz), 1.01 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 325 (3), 324 (23), 323 (100).

EXAMPLE 35 Preparation of 6-(2,4-Dichlorophenyl)-8-ethyl-9-(1-ethylpentyl)purine

A solution of 2,4-dichlorobenzeneboronic acid (572 mg, 3.00 mmol) and ethylene glycol (205 mg, 3.30 mmol) in benzene (20 mL) was heated to reflux with azeotropic removal of water for a period of 8 h. The resulting solution was cooled, and treated with 6-chloro-8-ethyl-9-(1-ethylpentyl)purine (see Example 2, Part C above; 562 mg, 2.00 mmol), thallium carbonate (1.03 g, 2.20 mmol) and tetrakis(triphenylphosphine)palladium (116 mg, 0.10 mmol). The resulting mixture was heated to reflux with stirring for 12 h, then cooled, filtered through celite and evaporated. The resulting residue was separated by column chromatography (silica gel, 10:90 ethyl acetate-hexane) to afford the title compound as a viscous oil (530 mg, 1.35 mmol, 68%). TLC R_(F) 0.31 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.94 (1H, s), 7.71 (1H, d, J=8.4 Hz), 7.58 (1H, d, J=1.8 Hz), 7.41 (1H, dd, J=8.4, 1.8 Hz), 4.27 (1H, br), 2.95 (2H, q, J=7.3 Hz), 2.41 (2H, br), 2.11-1.98 (2H, br), 1.42 (3H, t, J=7.3 Hz), 1.37-1.20 (3H, m), 1.09-0.99 (1H, m), 0.84 (3H, t, J=7.7 Hz), 0.82 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e calc'd for C₂₀H₂₅N₄Cl₂: 391.1456, found 391.1458; 395 (11), 394 (14), 393 (71), 392 (29), 391 (100).

EXAMPLE 38 Preparation of 3-(1-cyclopropylpropyl)-7-(2,4-dichlorophenyl)-2-ethyl-3H-imidazo[4,5-b]pyridine

Part A. 2,4-Dihydroxypyridine (15.0 g, 135 mmol) was heated in HNO₃ (85 mL) at 80° C. for 15-20 min at which time it went into solution. The temperature was maintained for 5 min and after cooling it was poured into ice/water (˜200 mL). The precipitated solid was collected and dried (19.0 g, 90% yield). ¹H NMR(300 MHz, dmso d6): 12.3-12.5 (1H, brs), 11.75-11.95 (1H, brs), 7.41 (1H, d J=7.3 Hz), 5.99 (1H, d J=7.3 Hz).

Part B. 4-Hydroxy-3-nitropyridone (8.0 g, 51.25 mmol) and cycloheptyl amine (6.8 mL, 53.4 mmol) were heated at reflux in methanol (100 mL) for 15 min. The solvent was stripped off and the residual solid was washed with 1:1 EWtOAc/hexanes and dried under vacuum. The cycloheptyl amine salt was stirred in POCl₃ (60 mL) for 40 h and poured into ice/water (˜600 mL). The precipitated produced was collected and dried under vacuum (7.0 g, 78% yield). ¹H NMR(300 MHz, dmso d6): 12.8-13.05 (1H, brs), 7.73 (1h, d J=7.0 Hz), 6.50 (1H, d J=7.0 Hz).

Part C. 4-Chloro-3-nitro-pyridone (0.5 g, 2.86 mmol) Ag₂CO₃ (0.83 g, 3 mmol) and benzyl bromide (0.36 mL, 3 mmol) were stirred in dry benzene (20 mL) at 60° C. for 5 h. The reaction mixture was filtered and stripped in vacuo. The residue was chromatographed on silica gel (10% EtOAc/hexanes eluent) to give the product (0.6 g, 79%). ¹H NMR(300 MHz, CDCl₃): 8.15 (1H, d J=4.0 Hz), 7.30-7.42 (5 H, m), 7.04 (1H, d J=4.0 Hz), 5.50 (2H, s).

Part D. 2-Benzyloxy-4-chloro-3-nitropyridine (0.5 g, 1.9 mmol), 2,4-dichlorophenylboronic acid (0.363 g, 1.9 mmol) Pd(PPh₃)₂Cl₂ (76 mg, 0.11 mmol) and Ba(OH)₂. 8H₂O (0.6 g, 1.9 mmol) were heated at reflux in 1,2-dimethoxyethane (6 mL), and water (6 mL) for 5 h. The mixture was partitioned between EtOAc (100 mL) and water (30 mL) and the EtOAc was washed with water, brine, dried and stripped in vacuo. The residue was chromatographed on silica gel (10% EtOAc/hexanes eluent) to give the product (370 mg, 52% yield). ¹H NMR(300 MHz, CDCl₃): 8.31 (1H, d J=5.1 Hz), 7.51 (1H, d J=2.2 Hz), 7.30-7.43 (6H, m), 7.20 (1H, d J=8.0 Hz), 6.91 (1H, d J=5.1 Hz), 5.56 (2h, s).

Part E. 2-Benzyloxy-4-(2,4-dichlorophenyl)-3-nitropyridine (1.65 g, 4.39 mmol) was stirred in CF₃CO₂H (5 mL) at 25° C. for 4 h. The CF₃CO₂H was stripped in vacuo and the residue was washed with 20% EtOAc/hexanes and used in the next reaction. ¹H NMR (300 MHz, CDCl₃): 7.62 (1H, d J=7.0 Hz), 7.53 (1H, d J=2.2 Hz), 7.34 (1H, dd J=7.0, 2.2 Hz), 7.22 (1H, d J=8.1 Hz), 6.33 (1H, d J=7.0 Hz).

Part F. 4-(2,4-dichlorophenyl)-3-nitropyridone (4.39 mmol) was heated at reflux in POCl₃ (5 mL) for 5 h. After cooling it was poured into ice/water (˜60 mL) and extracted with EtOAc (2×100 mL). The EtOAc was washed with with satNaHCO₃, brine, dried and stripped in vacuo. Used in the next reaction without further purification. ¹H NMR(300 MHz, CDCl₃): 8.60 (1H, d J=5.2 Hz), 7.54 (1H, d, J=2.2 Hz), 7.36 (1H, dd J=8.1, 2.2 Hz), 7.20 (1H, d J=8.1 Hz).

Part G. 2-Chloro-4-(2,4-dichlorophenyl)-3-nitropyridine (0.5 g, 1.65 mmol) 1-cyclopropylpropylamine hydrochloride (461 mg, 3.4 mmol) and diisopropyl ethylamine (1.26 mL, 0.72 mmol) were heated at reflux in CH₃CN (10 mL) for 64 h. The mixture was partitioned between EtOAc (70 mL) and water (40 mL). The aqueous layer was extracted with EtOAc (50 mL) and the combined EtOAc extracts washed with brine, dried and stripped in vacuo. The residue was chromatographed on silica gel (10% EtOAc/hexanes eluent) to give the product (310 mg, 51% yield). ¹H NMR(300 MHz, CDCl₃): 8.29 (1H, d J=4.7 Hz), 7.76 (1H, brd J=8.0 Hz), 7.46 (1H, d J=2.2 Hz), 7.32 (1H, dd J=8.5, 2.2 Hz), 7.15 (1H, d J=8.5 Hz), 3.72-3.85 (1H, m), 1.70-1.80 (2H, m), 0.90-1.08 (4H, m), 0.30-0.66 (4H, m).

Part H. 2-(1-cyclopropyl)propylamino-4-(2,4-dichlorophenyl)-3-nitropyridine (310 mg, 0.85 mmol) was dissolved in dioxane (8 mL) and water (8 mL) containing concNH₄OH (0.3 mL) was added, followed by Na₂S₂O₄ (1.1 g, 6.86 mmol). The reaction was stirred at 25° C. for 4 h and extracted with EtOAc (100 mL). The EtOAc was washed with brine, dried and stripped in vacuo. The residue was chromatographed on silica gel (25% EtOAc/hexanes and ˜1% conc NH₄OH eluent) to give the product (150 mg, 53% yield). ¹H NMR(300 MHz, CDCl₃): 7.73 (1H, d J=5.5 Hz), 7.53 (1H, d J=1.8 Hz), 7.35 (1H, dd J=8.1, 1.8 Hz), 7.24 (1H, d J=8.1 Hz), 6.35 (1H, d J=5.5 Hz), 4.3 (1H, brs), 3.5 (1H, brs), 3.42-3.55 (1H, m), 3.04 (2H, brs), 1.70-1.81 (2H, m), 0.88-1.08 (4H, m), 0.3-0.6 (4H, m).

Part I. 3-amino-2-(1-cyclopropyl)propylamino-4-(2,4-dichlorophenyl)-pyridine (140 mg, 0.42 mmol) was heated at reflux in propionic acid (5 mL) for 23 h. Then the mixture was diluted with water (50 mL), neutralized with solid NaHCO3 and basified with 50%NaOH. Then it was extracted with EtOAc (80 mL) and the EtOAc was dried and stripped in vacuo. The residue was chromatographed on silica gel (10% and 20% EtOAc/hexanes eluant) to give the product, which was crystallized from hexanes (70 mg, 45% yield) mp 118-119° C. ¹H NMR(300 MHz, CDCl₃): 8.31 (1H, d J=4.7 Hz), 7.62 (1H, d J=7.2 Hz), 7.55 (1H, d J=1.8 Hz), 7.37 (1H, dd J=7.2, 1.8 Hz), 7.23 (1H, d J=4.7 Hz), 3.50-3.70 (1H, brs), 2.87-2.96 (2H, q), 2.36-2.56 (1H, m), 2.18-2.35 (1H, m), 1.90-2.05 (1H, m), 1.38 (3H, t), 0.86 (3H, t), 0.75-0.84 (1H, m), 0.40-0.54 (1H, m), 0.15-0.25 (1H, m).

EXAMPLE 38A Preparation of 1-(1-cyclopropylpropyl)-4-(2,4-dichlorophenyl)-2-ethyl-1H-imidazo[4,5-c]pyridine

Part A. A mixture of 4-chloro-3-nitro-2-pyridone (2.0 g, 11.4 mmol), 1-cyclopropylpropyl amine hydrochloride (1.5 g, 11.4 mmol) and N,N-diisopropylethylamine (4.8 ml, 27.4 mmol) in CH₃CN (50 ml) were stirred at 25° C. for 16 h and at reflux for 4 h. After cooling it was stripped in vacuo, and the residue was partitioned between EtOAc (100 mL) and H2O (50 mL). The insolubles were separated, washed with H₂O and EtOAc and vacuum dried 1.51 g. The filtrate layers were separated and the aqueous layer was extracted with EtOAc (2×50 mL). The Combined extracts were washed with brine, dried over MgSO4, filtered and concd. in vacuo. The residue was washed with EtOAc (2×) and vacuum dried, to give 0.69 g, yellow solid. Combined wt. of 4-(1-cyclopropylpropyl)amino-3-nitro-2-pyridone 2.20 g, 81% yield. ¹H NMR(300 MHz, dmso d6): 11.19 (1H, br), 8.94 (1H, d J=8.8 Hz), 7.33 (1H, t J=6.9 Hz), 6.03 (1H, d J=7.7 Hz), 3.18-3.24 (1H, m), 1.60-1.74 (2H, m), 1.03-1.11(1H, m), 0.91 (3H, t), 0.40-0.60 (1H, m), 0.20-0.39 (1H, m).

Part B. 4-(1-Cyclopropyl)propylamino-3-nitro-2-pyridone (2.20 g, 9.27 mmol) was stirring in POCl₃ (15 mL) at 25° C. for 16 h. Then it was poured into ice/water (220 mL) and stirred until all the POCl₃ had reacted. The mixture was neutralized with solid NaHCO₃, filtered and extracted with EtOAc (3×60 mL). The combined organic extracts were washed with brine, dried over MgSO₄, filtered and stripped in vacuo. The crude oil was chromatographed on silica gel (100 g.) and eluted with a gradient from 10-20% EtOAc/hexane to afford 1.91 g 2-chloro-4-(1-cyclopropylpropyl)amino-3-nitropyridine, 81% yield. ¹H NMR(300 MHz, CDCl₃): 7.96 (1H, d J=6.3 Hz), 6.58 (1H, d J=6.3 Hz), 6.52 (1H, brd J=5.5 Hz), 2.90-3.00 (1H, m), 1.61-1.82 (2H, m), 1.01 (3H, t J=7.7 Hz), 0.90-1.02 (1H, m), 0.51-0.70 (2H, m), 0.21-0.34 (2H, m).

Part C. In a dried flask, under N₂, a mixture of 2-chloro-4-(1-cyclopropyl)propylamino-3-nitropyridine (730 mg, 2.85 mmol), 2,4-dichlorophenylboronic acid (544 mg, 2.85 mmol), dichlorobis(triphenylphosphine)palladium (III) (114 mg, 0.17 mmol) and barium hydroxide octahydrate (899 mg, 2.85 mmol) was heated at reflux in dimethoxyethane (8.6 mL) and H₂O (8.6 mL for 1.5 h. After cooling it was partitioned between EtOAc (100 mL) and water (20 mL) and filtered through celite. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organics were washed with brine, dried over MgSO₄, filtered and stripped in vacuo. The residue was chromatographed on silica gel (40 gm), and eluted with 30% EtOAc/hexane to afford a yellow oil, 1.00 g, 90% yield. ¹H NMR(300 MHz, CDCl₃): 8.24 (1H, d J=6.2 Hz), 7.87 (1H, brd J=7.3 Hz), 7.43 (1H, s), 7.34 (2H, s), 6.71 (1H, d J=6.2 Hz), 3.00-3.10 (1H, m), 1.70-1.85 (2H, m), 0.95-1.15 (4H, m), 0.50-0.71 (2H, m), 0.25-0.40 (2H, m).

Part D. The product from Part C (0.94 g, 2.57 mmol), by dissolving in dioxane (26 ml), H₂O (26 ml) and conc. NH₄OH (1.0 ml) while adding Na₂S₂O₄ and stirring at room temperature for 2 hrs. Added CH₂Cl₂ and extracted. Extracted the aqueous layer with CH₂Cl₂ (2×). Combined the organics and washed with brine, dried over MgSO4, filtered and concd. in vacuo to give a yellow solid, 1.01 g. It was carried over to the next reaction without purification.

Part E. The amine from Part D (1.01 g, 3.00 mmol) was cyclized by refluxing with propionic acid (27 ml, 365.45 mmol) for 8 hrs. Allowed to cool to RT. then basified with 1M NaOH and 50% NaOH. Extracted with EtOAc (2×60 mL) and CH₂Cl₂ (60 mL). Combined the organics and washed with H₂O, brine, dried over MgSO₄, filtered and concd. in vacuo. The crude oil was chromatographed on silica gel (40 g.) and eluted with 30% EtOAc/hexane to obtain a pale yellow solid (triturated from hexane), 520 mg, 46% yield. ¹H NMR(300 MHz, CDCl₃): 8.43 (1H, d J=5.8 Hz), 7.63 (1H, d J=8.1 Hz), 7.55 (1H, d J=1.8 Hz), 7.46 (1H, d J=5.8 Hz), 7.36 (1H, dd, J=8.1, 1.8 Hz), 3.40-3.50 (1H, m), 2.80-2.90 (2H, q J=7.7 Hz), 2.10-2.30 (2H, m), 1.50-1.64 (1H, m), 1.37 (3H, t J=7.3 Hz), 0.87 (3H, t J=7.3 Hz), 0.81-0.91 (1H, m), 0.48-0.58 (2H, m), 0.18-0.26 (1H, m). Elemental analysis calcd for C₂₀H₂₁N₃Cl₂: C, 64.18; H, 5.665; N, 11.23; found: C, 64.37; H, 5.66; N, 11.15.

EXAMPLE 831 Preparation of 6-(2-Chloro-4-methoxyphenyl)-9-dicyclopropylmethyl-8-ethylpurine

Part A. A solution of dicyclopropyl ketone (50 g) in absolute methanol (150 mL) in an autoclave vessel was charged with W4 Raney nickel (12 g, washed free of water and in methanol slurry) and then anhydrous ammonia (17 g). The mixture was subjected to 120 atm of hydrogen at 150-160° C. for 5 hours, then cooled and excess gasses purged. The resulting slurry was filtered through celite, and the filtrate was distilled to about one-third the original volume (atmospheric pressure, Vigreaux column). The pot solution was cooled to 0° C., diluted with 3 volumes diethyl ether, and treated with 4 N hydrochloric acid solution in anhydrous dioxane until precipitate formation ceased. The solid product (dicyclopropylmethylamine hydrochloride) was collected by filtration, washed with excess diethyl ether, and dried under vacuum (45.22 g, 306 mmol, 67%). ¹H NMR (300 MHz, methanol-d₄): d 1.94 (1H, t, J=9.3 Hz), 1.11-0.99 (2H, m), 0.75-0.59 (4H, m), 0.48-0.37 (4H, m). MS (NH₃-DCI): m/e 114. (5), 113 (100).

Part B. A solution of 5-amino-4,6-dichloropyrimidine (5.00 g, 30.5 mmol) and diisopropylethylamine (12.0 mL, 68.9 mmol) in ethanol (100 mL) was treated with the amine from Part A (3.81 g, 25.8 mmol), and heated to reflux for 72 h. The resulting mixture was cooled and poured into water (300 mL), which was extracted with ethyl acetate (2×300 mL). The extracts were washed with brine, combined, dried over sodium sulfate, filtered and evaporated. The residual oil was separated by column chromatography (30:70 ethyl acetate-hexane), and the desired product, 5-amino-4-chloro-6-dicyclopropylmethylaminopyrimidine, was triturated with warm ether-hexane, collected by filtration, and dried under vacuum (3.15 g, 13.2 mmol, 43%). m.p. 137-138° C. TLC R_(F) 0.17 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.01 (1H, s), 4.95 (1H, br d, J=7.3 Hz), 3.45 (1H, q, J=7.0 Hz), 3.37 (2H, br s), 1.06-0.94 (2H, m), 0.59-0.32 (8H, m). MS (NH₃-CI): m/e 243 (1), 242 (5), 241 (36), 240 (16), 239 (100).

Part C. A solution of the diamine from Part B (1.80 g, 7.54 mmol) and 1 drop concentrated hydrochloric acid in triethyl orthopropionate (12 mL) was heated to 100° C. for 6 hours. The excess orthoester was removed by distillation (partial vacuum, short-path), and the pot residue solidified to give the product, N-(4-chloro-6-dicyclopropylmethylaminopyrimidin-5-yl)-O-ethyl-propionimidate. ¹H NMR (300 MHz, CDCl₃): d 8.08 (1H, s), 4.84 (1H, br d, J=8.0 Hz), 4.35 (2H, br), 3.45 (1H, q, J=7.7 Hz), 2.14 (2H, q, J=7.3 Hz), 1.41 (3H, t, J=7.1 Hz), 1.08 (3H, t, J=7.7 Hz), 1.03-0.93 (2H, m), 0.58-0.27 (8H, m). MS (NH₃-CI): m/e 327 (1), 326 (7), 325 (36), 324 (21), 323 (100).

Part D. A solution of the imidate compound prepared in Part C above and p-toluenesulfonic acid monohydrate (50 mg) in diphenyl ether (10 mL) was heated to 170° C. for 2 hours. The resulting mixture was cooled and separated by column chromatography (silica gel, hexane to remove diphenyl ether, then 30:70 ethyl acetate-hexane) to afford the product, 6-chloro-9-dicyclopropylmethyl-8-ethylpurine, as an solid (1.42 g, 5.13 mmol, 68% for both steps C and D). m.p. 99-100° C. TLC R_(F) 0.26 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.63 (1H, s), 2.99 (2H, br), 1.92 (1H, br), 1.50 (3H, t, J=7.3 Hz), 0.87-0.78 (2H, m), 0.50-0.39 (4H, m), 0.20-0.10 (4H, m). MS (NH₃-CI): m/e 280 (6), 279 (36), 278 (19), 277 (100).

Part E. A solution of 4-amino-3-chlorophenol hydrochloride (18.6 g, 103 mmol) and sodium acetate (18.6 g, 227 mmol) in glacial acetic acid (200 mL) was heated to gentle reflux for 12 hours, then cooled and poured into 4 volumes water. This was neutralized with portionwise addition of sodium bicarbonate, and the resulting mixture was extracted with ethyl acetate (2×500 mL). The extracts were washed with brine, combined, dried over magnesium sulfate, filtered and evaporated. The resulting solid was triturated with warm ether; filtration and vacuum drying gave 4-acetamido-3-chlorophenol (16.1 g, 86.7 mmol, 84%). m.p. 128-129° C. TLC R_(F) 0.14 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, 4:1 CDCl₃.CD₃OD): d 7.66 (1H, d, J=8.8 Hz), 6.88 (1H, d, J=1.7 Hz), 6.74 (1H, dd, J=8.8, 1.7 Hz), 2.19 (3H, s). MS (H₂O-GC/MS): m/e 186 (100).

Part F. A solution of the phenol of Part E (14.6 g, 78.8 mmol), methyl iodide (10.0 mL, 160 mmol), and sodium carbonate (10.0 g, 94.3 mmol) in acetonitrile (200 mL) was heated to reflux for 48 hours, the cooled and poured into water (800 mL). This was extracted with ethyl acetate (2×800 mL), and the extracts were washed with brine, combined, dried over magnesium sulfate, filtered and evaporated. The resulting solid was recrystallized from ether-ethyl acetate to afford pure product, 2-chloro-4-methoxyacetanilide (13.2 g, 66.3 mmol, 84%), m. p. 118-119° C. (ether-ethyl acetate). TLC R_(F) 0.30 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.15 (1H, d, J=9.2 Hz), 7.39 (1H, br s), 6.92 (1H, d, J=3.0 Hz), 6.82 (1H, dd, J=9.2, 3.0 Hz), 3.78 (3H, s), 2.22 (3H, s). MS (NH₃-CI): m/e 219 (19), 217 (60), 202 (40), 201 (14), 200 (100).

Part G. A solution of the amide from Part F (10.1 g, 50.7 mmol) and sodium hydroxide (10 mL, 5 N, 50 mmol) in 95% ethanol (200 mL) was heated to 50° C. for 24 hours. Then, an additional 5 mL sodium hydroxide solution was added, and the mixture was heated to full reflux for an additional 48 hours. The solution was cooled and evaporated, and the residual material was partitioned between ether and water. The aqueous phase was extracted a second time with ether, and the extracts were washed with brine, combined, dried over sodium sulfate, filtered and evaporated. The resulting product, 2-chloro-4-methoxyaniline, was purified by elution through a short column of silica gel with 30:70 ethyl acetate-hexane, and the eluant was evaporated (7.98 g, 100%).

Part H. A solution of the aniline from Part G (7.98 g, 50 mmol) in conc. HCl (25 mL) was cooled to −5° C., and treated dropwise with a concentrated aqueous solution of sodium nitrite (3.80 g, 55.1 mmol). After 30 minutes, the mixture was charged with 15 mL cyclohexane and 15 mL dichloromethane, then treated dropwise with a concentrated aqueous solution of potassium iodide (16.6 g, 100 mmol). This mixture was allowed to stir for 4 hours, then was extracted with dichloromethane (2×100 mL). The extracts were washed in sequence with 1 N aqueous sodium bisulfite (100 mL) and brine (60 mL), then combined, dried over magnesium sulfate, filtered and evaporated to afford sufficiently pure product, 3-chloro-4-iodoanisole (7.00 g, 26.1 mmol, 52%). TLC R_(F) 0.39 (5:95 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.69 (1H, d, J=8.8 Hz), 7.03 (1H, d, J=3.0 Hz), 6.57 (1H, dd, J=8.8, 3.0 Hz), 3.78 (3H, s). MS (H₂O-GC/MS): m/e 269 (100).

Part I. A solution of the iodide compound from Part H (7.00 g, 26.1 mmol) in anhydrous tetrahydrofuran (50 mL) was cooled to −90° C., and treated with a hexane solution of n-butyllithium (16.5 mL, 1.6 M, 26.4 mmol). After 15 minutes, the solution was treated with triisopropylborate (6.10 mL, 26.4 mmol) and was allowed to warm to ambient temperature over 6 hours. The resulting mixture was treated with 6 N aqueous HCl (5 mL) and water (5 mL), which was stirred for 1 hour, then poured into water (100 mL) and extracted with ethyl acetate (2×100 mL). The extracts were washed in sequence with 1 N aqueous sodium bisulfite and brine (80 mL each), combined, dried over sodium sulfate, filtered and evaporated. The residual solid was triturated with 1:1 ether-hexane, collected by filtration and dried under vacuum to afford pure product, 2-chloro-4-methoxybenzeneboronic acid (3.05 g, 16.4 mmol, 63%). m.p. 191-195° C.

Part J. A solution of the chloride from Part D (770 mg, 2.78 mmol), the boronic acid from Part I (770 mg, 4.13 mmol), 2 N aqueous sodium carbonate solution (4 mL, 8 mmol) and triphenylphosphine (164 mg, 0.625 mmol) in DME (20 mL) was degassed by repeated cycles of brief vacuum pumping followed by nitrogen purging. To this was added palladium (II) acetate (35 mg, 0.156 mmol), and the mixture was degassed again and then heated to reflux for 14 hours. It was cooled, and poured into water (100 mL). This mixture was extracted with ethyl acetate (2×100 mL), and the extracts were washed in sequence with brine (60 mL), combined, dried over sodium sulfate, filtered and evaporated. The residual material was separated by column chromatography (silica gel, 15:85 ethyl acetate-hexane) to afford the title product as a solid. This was recrystallized to purity from hexane (791 mg, 2.07 mmol, 74%). m.p. 139-140° C. (hexane). TLC R_(F) 0.18 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.93 (1H, s), 7.74 (1H, d, J=8.4, Hz), 7.10 (1H, d, J=2.6 Hz), 6.96 (1H, dd, J=8.4, 2.6 Hz), 4.20 (1H, v br), 3.87 (3H, s), 2.97 (2H, v br), 2.00 (2H, v br), 1.44 (3H, br t, J=7 Hz), 0.89-0.79 (2H, m), 0.62-0.52 (2H, m), 0.51-0.40 (2H, m), 0.26-0.16 (2H, m). MS (NH₃-CI): m/e 387 (1), 386 (9), 385 (41), 384 (30), 383 (100). Analysis calc'd for C₂₁H₂₃ClN₄O: C, 65.87; H. 6.05; N, 14.63; found: C, 65.77; H, 6.03; N, 14.57.

In Table 1, Table 1A and Table 1B, melting point data correspond to compounds of Structure A unless otherwise indicated.

TABLE 1

(A) (B) (C) Ex. mp, No. R² X R³ R⁴ R⁵ R¹¹ R⁶ R^(1a) R^(1b) ° C.^(a) 1 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ 128-129 2 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ 99-100 3 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ oil 4 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₆H₅ — 5 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ c-C₃H₅ 143-145 6 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₆H₁₃ — 7 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₃H₇ 68-71 8 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ oil 9 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OH 196-197 10 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) oil 11 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(b) oil 12 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 13 CH₃ CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ 120-121 14 CH₃ CH₂ H CH₃ CH₃ H C₃ c-C₃H₅ (CH₂)₂OH 209-210 15 CH₃ CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ H 140-150 16 CH₃ CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ 186-187 17 CH₃ CH₂ H CH₃ CH₃ H CH₃ H C₆H₅ 121-122 18 CH₃ CH₂ H CH₃ CH₃ H CH₃ H 3-(CH₃O)-C₆H₄ oil 19 CH₃ CH₂ H CH₃ CH₃ H CH₃ H 2-Br-C₆H₄ 84-85 20 CH₃ CH₂ H CH₃ CH₃ H CH₃ H 4-CH₃—C₆H₄ 48-50 21 CH₃ CH₂ H CH₃ CH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 22 CH₃ CH₂ H CH₃ CH₃ H CH₃ H 2-(C₄H₉)—C₄H₉ — 23 CH₃ CH₂ H CH₃ CH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 24 CH₃ CH₂ H CH₃ CH₃ H CH₃ H (CH₂)₂OCH₃ — 25 CH₃ CH₂ H CH₃ CH₃ H CH₃ H CH₂OCH₃ — 26 CH₃ CH₂ H CH₃ CH₃ H CH₃ H C₂H₅ 120-123 27 CH₃ CH₂ H CH₃ CH₃ H CH₃ H C₃H₇ oil 28 CH₃ CH₂ H CH₃ CH₃ H CH₃ H C₄H₉ oil 29 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 30 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ OC₂H₅ 91-93 31 CH₃ CH₂ H CH₃ CH₃ H CH₃ H (CH₃)₂CH 120-121 32 CH₃ CH₂ H CH₃ CH₃ H CH₃ H O(CH₂)₂—OCH₃ — 33 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₂OCH₃ C₆H₅ — 34 CH₃ CH₂ H Cl Cl H H C₂H₅ C₂H₅ oil 35 CH₃ CH₂ H Cl Cl H H C₂H₅ C₄H₉ oil 36 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂OCH₃ — 37 CH₃ CH₂ H Cl Cl H H C₂H₅ C₆H₅ — 38 CH₃ CH₂ H Cl Cl H H C₂H₅ c-C₃H₅ oil (A) 118-119 (B) 125-126 (C) 39 CH₃ CH₂ H Cl Cl H H C₂H₅ C₆H₁₃ — 40 CH₃ CH₂ H Cl Cl H H C₂H₅ C₃H₇ oil 41 CH₃ CH₂ H Cl Cl H H C₂H₅ (CH₂)₂OCH₃ — 42 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂CN — 43 CH₃ CH₂ H Cl Cl H H C₂H₅ (CH₂)₂—(Q1)^(b) — 44 CH₃ CH₂ H Cl Cl H H C₂H₅ (CH₂)₂—(Q2)^(c) — 45 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂N(CH₃)₂ — 46 CH₃ CH₂ H Cl Cl H H c-C₃H₅ C₄H₉ — 47 CH₃ CH₂ H Cl Cl H H c-C₃H₅ CH₂OCH₃ — 48 CH₃ CH₂ H Cl Cl H H c-C₃H₅ C₆H₅ oil 49 CH₃ CH₂ H Cl Cl H H c-C₃H₅ c-C₃H₅ 156-157 50 CH₃ CH₂ H Cl Cl H H H C₆H₅ oil 51 CH₃ CH₂ H Cl Cl H H H 3-(CH₃O)—C₆H₄ oil 52 CH₃ CH₂ H Cl Cl H H H 2-Br—C₆H₄ — 53 CH₃ CH₂ H Cl Cl H H H 4-CH₃—C₆H₄ 114-115 54 CH₃ CH₂ H Cl Cl H H H 4-C₆H₅—C₆H₄ oil 55 CH₃ CH₂ H Cl Cl H H H 2-(C₄H₉)—C₄H₈ — 56 CH₃ CH₂ H Cl Cl H H H 3-(C₄H₉)—C₅H₁₀ — 57 CH₃ CH₂ H Cl Cl H H H (CH₂)₂OCH₃ — 58 CH₃ CH₂ H Cl Cl H H H CH₂OCH₃ — 59 CH₃ CH₂ H Cl Cl H H H C₂H₅ — 60 CH₃ CH₂ H Cl Cl H H H C₃H₇ — 61 CH₃ CH₂ H Cl Cl H H H C₄H₉ — 62 CH₃ CH₂ H Cl Cl H H CH₂OCH₂ CH₂OCH₃ — 63 CH₃ CH₂ H Cl Cl H H C₂H₅ OC₂H₅ — 64 CH₃ CH₂ H Cl Cl H H H OC₂H₅ — 65 CH₃ CH₂ H Cl Cl H H H O(CH₂)₂—OCH₃ — 66 CH₃ CH₂ H Cl Cl H H CH₂OCH₃ C₆H₅ — 67 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₂H₅ — 68 CH₃ CH₂ H CH₃ OCH₃ H CH₂ C₂H₅ C₄H₉ oil 69 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ CH₂OCH₃ — 70 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₅ — 71 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ c-C₃H₅ — 72 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₁₃ — 73 CH₃ CH₂ H CH₃ OCH₃ H CH₂ C₂H₅ C₃H₇ — 74 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 75 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ CH₂CN — 76 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 77 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 78 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 79 CH₃ CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ C₄H₉ — 80 CH₃ CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ CH₂OCH₃ — 81 CH₃ CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ C₆H₅ — 82 CH₃ CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ c-C₃H₅ 167-169 83 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H C₆H₅ 134-135 84 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H 3-(CH₃O)—C₆H₄ — 85 CH₃ CH₃ H CH₃ OCH₃ H CH₃ H 2-Br—C₆H₄ — 86 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H 4-CH₃—C₆H₄ — 87 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 88 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H 2-(C₄H₉)—C₄H₈ — 89 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 90 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H (CH₂)₂OCH₃ — 91 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H CH₂OCH₂ — 92 CH₃ CH₂ H CH OCH₃ H CH₃ H C₂H₅ — 93 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H C₃H₇ — 94 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H C₄H₉ — 95 CH₃ CH₂ H CH₃ OCH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 96 CH₃ CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ OC₂H₅ — 97 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H OC₂H₅ — 98 CH₃ CH₂ H CH₃ OCH₃ H CH₃ H O(CH₂)₂—OCH₃ — 99 CH₃ CH₂ H CH₃ OCH₃ H CH₃ CH₂OCH₃ C₆H₅ — 100 CH₃ CH₂ H CH₃ CH₃ H CH₃ H CH₃ 138-140 101 H CH₂ H CH₃ CH₂ H CH₂ C₂H₅ C₂H₅ 198-199 102 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ 147-148 103 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ 140-142 104 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₆H₅ — 105 H CH₃ H CH₃ CH₃ H CH₃ C₂H₅ c-C₃H₅ — 106 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₆H₁₃ — 107 H CH₂ H CH₃ CH₂ H CH₃ C₂H₅ C₃H₅ — 108 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 109 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂CN — 110 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 111 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 112 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 113 H CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 114 H CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ CH₂OCH₃ — 115 H CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ C₆H₅ — 116 H CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 117 H CH₂ H CH₃ CH₃ H CH₃ H C₆H₅ — 118 H CH₂ H CH₃ CH₃ H CH₃ H 3-(CH₃O)—C₆H₄ — 119 H CH₂ H CH₃ CH₃ H CH₃ H 2-Br-C₆H₄ — 120 H CH₂ H CH₃ CH₃ H CH₃ H 4-CH₃—C₆H_(4 —) 121 H CH₂ H CH₃ CH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 122 H CH₂ H CH₃ CH₃ H CH₃ H 3-C₇H₅ oil 123 H CH₂ H CH₃ CH₃ H CH₃ H 2-(C₂H₅)—C₆H₁₂ oil 124 H CH₂ H CH₃ CH₃ H CH₃ H (CH₂)₂OCH₃ — 125 H CH₂ H CH₃ CH₃ H CH₃ H CH₂OCH₃ — 126 H CH₂ H CH₃ CH₃ H CH₃ H C₂H₅ — 127 H CH₂ H CH₃ CH₃ H CH₃ H C₃H₇ — 128 H CH₂ H CH₃ CH₃ H CH₃ H C₄H₉ — 129 H CH₂ H CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 130 H CH₂ H CH₃ CH₃ H CH₃ C₂H₅ OC₂H₅ — 131 H CH₂ H CH₃ CH₃ H CH₃ H OC₂H₅ — 132 H CH₂ H CH₃ CH₃ H CH₃ H O(CH₂)₂—OCH₃ — 133 H CH₂ H CH₃ CH₃ H CH₃ CH₂OCH₃ C₆H₅ — 134 H CH₂ H Cl Cl H H C₂H₅ C₂H₅ — 135 H CH₂ H Cl Cl H H C₂H₅ C₄H₉ — 136 H CH₂ H Cl Cl H H C₂H₅ CH₂OCH₃ — 137 H CH₂ H Cl Cl H H C₂H₅ C₆H₅ — 138 H CH₂ H Cl Cl H H C₂H₅ c-C₃H₅ — 139 H CH₂ H Cl Cl H H C₂H₅ C₆H₁₃ — 140 H CH₂ H Cl Cl H H C₂H₅ C₃H₇ — 141 H CH₂ H Cl Cl H H C₂H₅ (CH₂)₂OCH₃ — 142 H CH₂ H Cl Cl H H C₂H₅ CH₂CN — 143 H CH₂ H Cl Cl H H C₂H₅ (CH₂)₂—(Q1)^(b) — 144 H CH₂ H Cl Cl H H C₂H₅ (CH₂)₂—(Q2)^(c) — 145 H CH₂ H Cl Cl H H C₂H₅ CH₂N(CH₃)₂ — 146 H CH₂ H Cl Cl H H c-C₃H₅ C₄H₉ — 147 H CH₂ H Cl Cl H H c-C₃H₅ CH₂OCH₃ — 148 H CH₂ H Cl Cl H H c-C₃H₅ C₆H₅ — 149 H CH₂ H Cl Cl H H c-C₃H₅ c-C₃H₅ — 150 H CH₂ H Cl Cl H H H C₆H₅ — 151 H CH₃ H Cl Cl H H H 3-(CH₃O)-C₆H₄ — 152 H CH₂ H Cl Cl H H H 2-(C₄H₉)—C₆H₄ — 153 H CH₂ H Cl Cl H H H 4-CH₃—C₆H₄ — 154 H CH₂ H Cl Cl H H H 4-C₆H₅—C₆H₄ — 155 H CH₂ H Cl Cl H H H 2-(C₄H₉)—C₄H₉ — 156 H CH₂ H Cl Cl H H H 3-(C₄H₉)—C₅H₁₀ — 157 H CH₂ H Cl Cl H H H (CH₂)₂OCH₃ — 158 H CH₂ H Cl Cl H H H CH₂OCH₃ — 159 H CH₂ H Cl Cl H H H C₂H₅ — 160 H CH₂ H Cl Cl H H H C₃H₇ — 161 H CH₂ H Cl Cl H H H C₄H₉ — 162 H CH₂ H Cl Cl H H CH₂OCH₃ CH₂OCH₃ — 163 H CH₂ H Cl Cl H H C₂H₅ OC₂H₅ — 164 H CH₂ H Cl Cl H H H OC₂H₅ — 165 H CH₂ H Cl Cl H H H C(CH₂)₂—OCH₃ — 166 H CH₂ H Cl Cl H H CH₂OCH₃ C₆H₅ — 167 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₂H₅ — 168 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₄H₉ — 169 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ CH₂OCH₃ — 170 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₅ — 171 H CH₂ H CH₃ OCH₃ H CH₂ C₂H₅ c-C₃H₅ — 172 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₁₃ — 173 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ C₃H₅ — 174 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 175 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ CH₂CN — 176 H CH₂ H CH₃ OCH₃ H CH₂ C₂H₅ (CH₂)₂—(Q1)^(b) — 177 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 178 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 179 H CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ C₄H₉ — 180 H CH₂ H CH₃ OCH₃ H CH₃ c-C₃H₅ CH₂OCH₃ — 181 H CH₂ H CH₃ OCH₂ H CH₃ c-C₃H₅ C₆H₅ — 182 H CH₂ H CH₃ OCH₂ H CH₃ c-C₃H₅ c-C₃H₅ — 183 H CH₂ H CH₃ OCH₃ H CH₃ H C₆H₅ — 184 H CH₂ H CH₃ OCH₃ H CH₃ H 3-(CH₃O)—C₆H₄ — 185 H CH₂ H CH₃ OCH₃ H CH₃ H 2-Br—C₆H₄ — 186 H CH₂ H CH₃ OCH₃ H CH₃ H 4-CH₃—C₆H₄ — 187 H CH₃ H CH₃ OCH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 188 H CH₂ H CH₃ OCH₃ H CH₃ H 2-(C₄H₉)—C₄H₈ — 189 H CH₂ H CH₃ OCH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 190 H CH₂ H CH₃ OCH₃ H CH₃ H (CH₂)₂OCH₃ — 191 H CH₂ H CH₃ OCH₃ H CH₃ H CH₃OCH₃ — 192 H CH₂ H CH₃ OCH₃ H CH₃ H C₂H₅ — 193 H CH₂ H CH₃ OCH₃ H CH₃ H C₃H₇ — 194 H CH₂ H CH₃ OCH₃ H CH₃ H C₄H₉ — 195 H CH₂ H CH₃ OCH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 196 H CH₂ H CH₃ OCH₃ H CH₃ C₂H₅ OC₂H₅ — 197 H CH₂ H CH₃ OCH₃ H CH₃ H OC₂H₅ — 198 H CH₂ H CH₃ OCH₃ H CH₃ H O(CH₂)₂—OCH₃ — 199 H CH₂ H CH₃ OCH₃ H CH₃ CH₂OCH₂ C₆H₅ — 200 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₂ C₂H₅ 98-100 201 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 202 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ oil 203 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 204 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₆H₅ — 205 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ c-C₃H₅ — 206 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₆H₁₃ — 207 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₃H₇ — 208 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ (CH₃)₂OCH₃ — 209 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ CH₂CN — 210 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 211 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 212 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 213 CH₃ O H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 214 CH₃ O H CH₃ CH₃ H CH₃ c-C₃H₅ CH₂OCH₃ — 215 CH₃ O H CH₃ CH₃ H CH₃ c-C₃H₅ C₆H₅ — 216 CH₃ O H CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 217 CH₃ O H CH₃ CH₃ H CH₃ H C₆H₅ — 218 CH₃ O H CH₃ CH₃ H CH₃ H 3-(CH₃C)—O₆H₄ — 219 CH₃ O H CH₃ CH₃ H CH₃ H 2-Br—C₆H₄ — 220 CH₃ O H CH₃ CH₃ H CH₃ H 4-CH₃—C₆H₄ — 221 CH₃ O H CH₃ CH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 222 CH₃ O H CH₃ CH₃ H CH₃ H 2-(C₄H₉)—C₄H₆ — 223 CH₃ O H CH₃ CH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 224 CH₃ O H CH₃ CH₃ H CH₃ H (CH₂)₃OCH₃ — 225 CH₃ O H CH₃ CH₃ H CH₃ H CH₂OCH₃ — 226 CH₃ O H CH₃ CH₃ H CH₃ H C₂H₅ — 227 CH₃ O H CH₃ CH₃ H CH₃ H C₃H₇ — 228 CH₃ O H CH₃ CH₃ H CH₃ H C₄H₉ — 229 CH₃ O H CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 230 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ OC₂H₅ — 231 CH₃ O H CH₃ CH₃ H CH₃ C₃H₇ OC₂H₅ — 232 CH₃ O H CH₃ CH₃ H CH₃ H O(CH₂)₂—OCH₃ — 233 CH₃ O H CH₃ CH₃ H CH₂ CH₂OCH₃ C₆H₅ — 234 CH₃ O H Cl Cl H H C₂H₅ C₂H₅ — 235 CH₃ O H Cl Cl H H C₂H₅ C₄H₉ — 236 CH₃ O H Cl Cl H H C₂H₅ CH₂OCH₃ — 237 CH₃ O H Cl Cl H H C₂H₅ C₆H₅ — 238 CH₃ O H Cl Cl H H C₂H₅ c-C₃H₅ — 239 CH₃ O H Cl Cl H H C₂H₅ C₆H₁₃ — 240 CH₃ O H Cl Cl H H C₂H₅ C₃H₇ — 241 CH₃ O H Cl Cl H H C₂H₅ (CH₂)₂OCH₃ — 242 CH₃ O H Cl Cl H H C₂H₅ CH₂CN — 243 CH₃ O H Cl Cl H H C₂H₅ (CH₂)₂—(Q1)^(b) — 244 CH₃ O H Cl Cl H H C₂H₅ (CH₂)₂—(Q2)^(c) — 245 CH₃ O H Cl Cl H H C₂H₅ CH₂N(CH₃)₂ — 246 CH₃ O H Cl Cl H H c-C₃H₅ C₄H₉ — 247 CH₃ O H Cl Cl H H c-C₃H₅ CH₂OCH₃ — 248 CH₃ O H Cl Cl H H c-C₃H₅ C₆H₅ — 249 CH₃ O H Cl Cl H H c-C₃H₅ c-C₃H₅ 132-134 250 CH₃ O H Cl Cl H H H C₆H₅ — 251 CH₃ O H Cl Cl H H H 3-(CH₃O)—C₆H₄ — 252 CH₃ O H Cl Cl H H H 2-Br-C₆H₄ — 253 CH₃ O H Cl Cl H H H 4-CH₃—C₆H₄ — 254 CH₃ O H Cl Cl H H H 4-C₆H₅—C_(6H) ₄ — 255 CH₃ O H Cl Cl H H H 2-(C₄H₉)—C₄H₉ — 256 CH₃ O H Cl Cl H H H 3-(C₄H₉)—C₅H₁₀ — 257 CH₃ O H Cl Cl H H H (CH₂)₂OCH₃ — 258 CH₃ O H Cl Cl H H H CH₂OCH₃ — 259 CH₃ O H Cl Cl H H H C₂H₅ — 260 CH₃ O H Cl Cl H H H C₃H₇ — 261 CH₃ O H Cl Cl H H H C₄H₉ — 262 CH₃ O H Cl Cl H H CH₂OCH₃ CH₂OCH₃ — 263 CH₃ O H Cl Cl H H C₂H₅ OC₂H₅ — 264 CH₃ O H Cl Cl H H H OC₂H₅ — 265 CH₃ O H Cl Cl H H H O(CH₂)₂—OCH₃ — 266 CH₃ O H Cl Cl H H CH₂OCH₃ C₆H₅ — 267 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ C₂H₅ — 268 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ C₄H₉ — 269 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ CH₂OCH₃ — 270 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₅ — 271 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ c-C₃H₅ — 272 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₁₃ — 273 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ C₃H₇ — 274 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 275 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ CH₂CN — 276 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 277 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 278 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 279 CH₃ O H CH₃ OCH₃ H CH₃ c-C₃H₅ C₄H₉ — 280 CH₃ O H CH₃ OCH₃ H CH₃ c-C₃H₅ CH₂OCH₃ — 281 CH₃ O H CH₃ OCH₃ H CH₃ c-C₃H₅ C₆H₅ — 282 CH₃ O H CH₃ OCH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 283 CH₃ O H CH₃ OCH₃ H CH₃ H C₆H₅ — 284 CH₃ O H CH₃ OCH₃ H CH₃ H 3-(CH₃O)—C₆H₄ — 285 CH₃ O H CH₃ OCH₃ H CH₃ H 2-Br—C₆H₄ — 286 CH₃ O H CH₃ OCH₃ H CH₃ H 4-CH₃—C₆H₄ — 287 CH₃ O H CH₃ OCH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 288 CH₃ O H CH₃ OCH₃ H CH₃ H 2-(C₄H₉)—C₄H₉ — 289 CH₃ O H CH₃ OCH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 290 CH₃ O H CH₃ OCH₃ H CH₃ H (CH₂)₂OCH₃ — 291 CH₃ O H CH₃ OCH₃ H CH₃ H CH₂OCH₃ — 292 CH₃ O H CH₃ OCH₃ H CH₃ H C₂H₅ — 293 CH₃ O H CH₃ OCH₃ H CH₃ H C₃H₇ — 294 CH₃ O H CH₃ OCH₃ H CH₃ H C₄H₉ — 295 CH₃ O H CH₃ OCH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 296 CH₃ O H CH₃ OCH₃ H CH₃ C₂H₅ OC₂H₅ — 297 CH₃ O H CH₃ OCH₃ H CH₃ H OC₂H₅ — 298 CH₃ O H CH₃ OCH₃ H CH₃ H O(CH₃)₂—OCH₃ — 299 CH₃ O H CH₃ OCH₃ H CH₃ CH₂OCH₃ C₆H₅ — 300 CH₃ CH₂ CH₃ H Cl H H c-C₃H₅ c-C₃H₅ 106-109 301 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 302 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ — 303 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 304 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ C₆H₅ — 305 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ c-C₃H₅ — 306 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ C₆H₁₃ — 307 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ C₃H₇ — 308 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 309 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ CH₂CN — 310 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 311 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ (CH₃)₂—(Q2)^(c) — 312 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 313 CH₃ S H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 314 CH₃ S H CH₃ CH₃ H CH₃ c-C₃H₅ CH₂OCH₃ — 315 CH₃ S H CH₃ CH₃ H CH₃ c-C₃H₅ C₆H₅ — 316 CH₃ S H CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 317 CH₃ S H CH₃ CH₃ H CH₃ H C₆H₅ — 318 CH₃ S H CH₃ CH₃ H CH₃ H 3-(CH₃O)—C₆H₄ — 319 CH₃ S H CH₃ CH₃ H CH₃ H 2-Br—C₆H₄ — 320 CH₃ S H CH₃ CH₃ H CH₃ H 4-CH₃—C₆H₄ — 321 CH₃ S H CH₃ CH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 322 CH₃ S H CH₃ CH₃ H CH₃ H 2-(C₄H₉)—C₄H₉ — 323 CH₃ S H CH₃ CH₃ H CH₃ H 3-(C₄H₉)—C₅H₁₀ — 324 CH₃ S H CH₃ CH₃ H CH₃ H (CH₂)₂OCH₃ — 325 CH₃ S H CH₃ CH₃ H CH₃ H CH₂OCH₃ — 326 CH₃ S H CH₃ CH₃ H CH₃ H C₂H₅ — 327 CH₃ S H CH₃ CH₃ H CH₃ H C₃H₇ — 328 CH₃ S H CH₃ CH₃ H CH₃ H C₄H₉ — 329 CH₃ S H CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 330 CH₃ S H CH₃ CH₃ H CH₃ C₂H₅ OC₂H₅ — 331 CH₃ S H CH₃ CH₃ H CH₃ H OC₂H₅ — 332 CH₃ S H CH₃ CH₃ H CH₃ H O(CH₂)₂—OCH₃ — 333 CH₃ S H CH₃ CH₃ H CH₃ CH₂OCH₃ C₆H₅ — 334 CH₃ S H Cl Cl H H C₂H₅ C₂H₅ — 335 CH₃ S H Cl Cl H H C₂H₅ C₄H₉ — 336 CH₃ S H Cl Cl H H C₂H₅ CH₂OCH₃ — 337 CH₃ S H Cl Cl H H C₂H₅ C₆H₅ — 338 CH₃ S H Cl Cl H H C₂H₅ c-C₃H₅ — 339 CH₃ S H Cl Cl H H C₂H₅ C₆H₁₃ — 340 CH₃ S H Cl Cl H H C₂H₅ C₃H₇ — 341 CH₃ S H Cl Cl H H C₂H₅ (CH₂)₂OCH₃ — 342 CH₃ S H Cl Cl H H C₂H₅ CH₂CN — 343 CH₃ S H Cl Cl H H C₂H₅ (CH₂)₂—(Q1)^(b) — 344 CH₃ S H Cl Cl H H C₂H₅ (CH₂)₂—(Q2)^(c) — 345 CH₃ S H Cl Cl H H C₂H₅ CH₂N(CH₃)₂ — 346 CH₃ S H Cl Cl H H c-C₃H₅ C₄H₉ — 347 CH₃ S H Cl Cl H H c-C₃H₅ CH₂OCH₃ — 348 CH₃ S H Cl Cl H H c-C₃H₅ C₆H₅ — 349 CH₃ S H Cl Cl H H c-C₃H₅ c-C₃H₅ — 350 CH₃ S H Cl Cl H H H C₆H₅ — 351 CH₃ S H Cl Cl H H H 3-(CH₂O)—C₆H₅ — 352 CH₃ S H Cl Cl H H H 2-Br—C₆H₅ — 353 CH₃ S H Cl Cl H H H 4-CH₃—C₆H₄ — 354 CH₃ S H Cl Cl H H H 4-C₆H₅—C₆H₄ — 355 CH₃ S H Cl Cl H H H 2-(C₄H₉)—C₄H₈ — 356 CH₃ S H Cl Cl H H H 3-(C₄H₉)—C₅H₁₀ — 357 CH₃ S H Cl Cl H H H (CH₂)₂OCH₃ — 358 CH₃ S H Cl Cl H H H CH₂OCH₃ — 359 CH₃ S H Cl Cl H H H C₂H₅ — 360 CH₃ S H Cl Cl H H H C₃H₇ — 361 CH₃ S H Cl Cl H H H C₄H₉ — 362 CH₃ S H Cl Cl H H CH₂OCH₃ CH₂OCH₃ — 363 CH₃ S H Cl Cl H H C₂H₅ OC₂H₅ — 364 CH₃ S H Cl Cl H H H OC₂H₅ — 365 CH₃ S H Cl Cl H H H O(CH₂)₂—OCH₃ — 366 CH₃ S H Cl Cl H H CH₂OCH₃ C₆H₅ — 367 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ C₂H₅ — 368 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ C₄H₉ — 369 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ CH₂OCH₃ — 370 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₅ — 371 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ c-C₃H₅ — 372 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ C₆H₁₃ — 373 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ C₃H₇ — 374 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 375 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ CH₂CN — 376 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q1)^(b) — 377 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ (CH₂)₂—(Q2)^(c) — 378 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ CH₂N(CH₃)₂ — 379 CH₃ S H CH₃ OCH₃ H CH₃ c-C₃H₅ C₄H₉ — 380 CH₃ S H CH₃ OCH₃ H CH₃ c-C₃H₅ CH₂OCH₃ — 381 CH₃ S H CH₃ OCH₃ H CH₃ c-C₃H₅ C₆H₅ — 382 CH₃ S H CH₃ OCH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 383 CH₃ S H CH₃ OCH₃ H CH₃ H C₆H₅ — 384 CH₃ S H CH₃ OCH₃ H CH₃ H 3-(CH₃O)—C₆H₅ — 385 CH₃ S H CH₃ OCH₃ H CH₃ H 2-Br—C₆H₄ — 386 CH₃ S H CH₃ OCH₃ H CH₃ H 4-CH₂—C₆H₄ — 387 CH₃ S H CH₃ OCH₃ H CH₃ H 4-C₆H₅—C₆H₄ — 388 CH₃ S H CH₃ OCH₃ H CH₃ H 2-(C₄H₉)—C₄H₉ — 389 CH₃ S H CH₃ OCH₃ H Ch₃ H 3-(C₄H₉)—C₅H₁₀ — 390 CH₃ S H CH₃ OCH₃ H CH₃ H (CH₂)₂OCH₃ — 391 CH₃ S H CH₃ OCH₃ H CH₃ H CH₂OCH₃ — 392 CH₃ S H CH₃ OCH₃ H CH₃ H C₂H₅ — 393 CH₃ S H CH₃ OCH₃ H CH₃ H C₃H₇ — — 394 CH₃ S H CH₃ OCH₃ H CH₃ H C₄H₉ — 395 CH₃ S H CH₃ OCH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 396 CH₃ S H CH₃ OCH₃ H CH₃ C₂H₅ OC₂H₅ — 397 CH₃ S H CH₃ OCH₃ H CH₃ H OC₂H₅ — 398 CH₃ S H CH₃ OCH₃ H CH₃ H O(CH₂)₂—OCH₃ — 399 CH₃ S H CH₃ OCH₃ H CH₃ CH₂OCH₃ C₆H₅ — 400 CH₃ CH₂ H Cl Cl H CH₃ C₃H₇ c-C₃H₅ 153-156 401 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 402 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ 107-108 403 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ 187-188 404 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ H C₄H₉ oil 405 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ 98-99 406 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ H C₆H₅ 149-150 407 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 408 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ H (CH₂)₂OCH₃ — 409 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 410 CH₃ CH₂ CH₃ CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 411 CH₃ CH₂ H CH₃ Cl H H C₂H₅ C₂H₅ — 412 CH₃ CH₂ H CH₃ Cl H H c-C₃H₅ C₄H₉ — 413 CH₃ CH₂ H CH₃ Cl H H c-C₃H₅ c-C₃H₅ 139-140 414 CH₃ CH₂ H CH₃ Cl H H CH₃ C₃H₇ oil (A, C) 415 CH₃ CH₂ H CH₃ Cl H H C₂H₅ C₄H₉ oil 416 CH₃ CH₂ H CH₃ Cl H H H C₆H₅ — 417 CH₃ CH₂ H CH₃ Cl H H C₂H₅ (CH₂)₂OCH₃ — 418 CH₃ CH₂ H CH₃ Cl H H H (CH₂)₂OCH₃ — 419 CH₃ CH₂ H CH₃ Cl H H CH₂OCH₃ CH₂OCH₃ — 420 CH₃ CH₂ H CH₃ Cl H H C₂H₅ CH₂OCH₃ — 421 CH₃ CH₂ H Cl CH₃ H H C₂H₅ C₂H₅ — 422 CH₃ CH₂ H Cl CH₃ H H c-C₃H₅ C₄H₉ — 423 CH₃ CH₂ H Cl CH₃ H H c-C₃H₅ c-C₃H₅ 177-178 424 CH₃ CH₂ H Cl CH₃ H H CH₃ C₃H₇ oil 425 CH₃ CH₂ H Cl CH₃ H H C₂H₅ C₄H₉ — 426 CH₃ CH₂ H Cl CH₃ H H H C₆H₅ — 427 CH₃ CH₂ H Cl CH₃ H H C₂H₅ (CH₂)₂OCH₃ — 428 CH₃ CH₂ H Cl CH₃ H H H (CH₂)₂OCH₃ — 429 CH₃ CH₂ H Cl CH₃ H H CH₂OCH₃ CH₂OCH₃ — 430 CH₃ CH₂ H Cl CH₃ H H C₂H₅ CH₂OCH₃ — 431 CH₃ CH₂ H Cl Cl H OCH₃ C₃H₇ c-C₃H₅ 141-144 432 CH₃ CH₂ H CH₃ CH₃ H OCH₃ C₂H₅ C₃H₇ 108-110 433 CH₃ CH₂ H Cl Cl H CH₃ c-C₃H₅ c-C₃H₅ 194-195 434 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ c-C₃H₅CH₂ oil 435 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OH 155-157 436 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ c-C₃H₅CH₂ oil 437 CH₃ CH₂ H CH₃ OCH₃ H H CH₃ C₃H₇ oil 438 CH₃ CH₂ H CH₃ OCH₃ H H H 4-(CH₃O)—C₆H₄ oil 439 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ c-C₃H₅ oil 440 CH₃ CH₂ H CH₃ OCH₃ H H CH₃ C₅H₁₁ oil 441 CH₃ CH₂ H Cl NMe₂ H H C₂H₅ C₂H₅ — 442 CH₃ CH₂ H Cl NMe₂ H H c-C₃H₅ C₄H₉ — 443 CH₃ CH₂ H Cl NMe₂ H H c-C₃H₅ c-C₃H₅ — 444 CH₃ CH₂ H Cl NMe₂ H H H C₃H₇ — 445 CH₃ CH₂ H Cl NMe₂ H H C₂H₅ C₄H₉ — 446 CH₃ CH₂ H Cl NMe₂ H H H C₆H₅ — 447 CH₃ CH₂ H Cl NMe₂ H H C₂H₅ (CH₂)₂OCH₃ — 446 CH₃ CH₂ H Cl NMe₂ H H H (CH₂)₂OCH₃ — 449 CH₃ CH₂ H Cl NMe₂ H H CH₂OCH₃ CH₂OCH₃ — 450 CH₃ CH₂ H Cl NMe₂ H H C₂H₅ CH₂OCH₃ — 451 CH₃ CH₂ H CH₃ NMe₂ H H C₂H₅ C₂H₅ — 452 CH₃ CH₂ H CH₃ NMe₂ H H c-C₃H₅ C₄H₉ — 453 CH₃ CH₂ H CH₃ NMe₂ H H c-C₃H₅ c-C₃H₅ — 454 CH₃ CH₂ H CH₃ NMe₂ H H H C₃H₇ — 455 CH₃ CH₂ H CH₃ NMe₂ H H C₂H₅ C₄H₉ — 456 CH₃ CH₂ H CH₃ NMe₂ H H H C₆H₅ — 457 CH₃ CH₂ H CH₃ NMe₂ H H C₂H₅ (CH₂)₂OCH₃ — 458 CH₃ CH₂ H CH₃ NMe₂ H H H (CH₂)₂OCH₃ — 459 CH₃ CH₂ H CH₃ NMe₂ H H CH₂OCH₃ CH₂OCH₃ — 460 CH₃ CH₂ H CH₃ NMe₂ H H C₂H₅ CH₂OCH₂ — 461 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 462 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 463 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 464 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ H C₃H₇ — 465 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ — 466 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ H C₆H₅ — 467 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 468 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ H (CH₂)₂OCH₃ — 469 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 470 CH₃ CH₂ NMe₂ CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 471 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 472 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 473 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 474 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ H C₃H₇ — 475 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ 92-95 476 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ H C₆H₅ — 477 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 478 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ H (CH₂)₂OCH₃ — 479 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 480 C₂H₅ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 481 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 482 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 483 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 484 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ H C₃H₇ — 485 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ C₂H₅ C₄H₉ — 486 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ H C₆H₅ — 487 CH₃ CHCH₃ H CH₃ C₂H₅ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 488 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ H (CH₂)₂OCH₃ — 489 CH₃ CHCH₃ H CH₃ CH₃ H CH₃ CH₂OCH₃ CH₂OCH₃ — 490 CH₃ CHCH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OCH₃ — 491 CH₃ CH₂ H CH₃ CH₃ H H C₂H₅ C₂H₅ 96-97 492 CH₃ CH₂ H CH₃ CH₃ H H c-C₃H₅ C₄H₉ — 493 CH₃ CH₂ H CH₃ CH₃ H H c-C₃H₅ c-C₃H₅ 149-150 494 CH₃ CH₂ H CH₃ CH₃ H H H C₃H₇ 99-100 495 CH₃ CH₂ H CH₃ CH₃ H H C₂H₅ C₄H₉ — 496 CH₃ CH₂ H CH₃ CH₃ H H H C₆H₅ — 497 CH₃ CH₂ H CH₃ CH₃ H H C₂H₅ (CH₂)₂OCH₃ — 498 CH₃ CH₂ H CH₃ CH₃ H H H (CH₂)₂OCH₃ — 499 CH₃ CH₂ H CH₃ CH₃ H H CH₂OCH₃ CH₂OCH₃ — 500 CH₃ CH₂ H CH₃ CH₃ H H C₂H₅ CH₂OCH₂ — 501 CH₃ CH₂ H CH₃ CH₃ H H CH₃ C₃H₇ — 502 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃ C₄H₉ oil 503 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃ C₅H₁₁ oil 504 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ 2-C₄H₉ 109-110 505 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OC₂H₅ — 506 CH₃ CH₂ H Cl Cl H H CH₃ C₃H₇ oil (A,B,C) 507 CH₃ CH₂ H Cl Cl H H CH₃ C₄H₉ oil 508 CH₃ CH₂ H Cl Cl H H CH₃ C₅H₁₁ — 509 CH₃ CH₂ H Cl Cl H H C₂H₅ 2-C₄H₉ — 510 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂OC₂H₅ — 511 CH₃ CH₂ H Cl CF₃ H H C₂H₅ c-C₃H₅ oil (A) 78-80 (B) 116-117 (C) 512 CH₃ CH₂ H Cl CF₃ H H c-C₃H₅ c-C₃H₅ 145-146 513 CH₃ CH₂ H Cl CF₃ H H C₂H₅ C₄H₉ oil 514 CH₃ CH₂ H Cl CF₃ H H C₂H₅ C₂H₅ oil 515 CH₃ CH₂ H Cl CF₃ H H C₂H₅ CH₂OC₂H₅ — 516 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅ c-C₃H₅ — 517 CH₃ CH₂ H OCH₃ Cl H Cl c-C₃H₅ c-C₃H₅ 183-184 518 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅ C₄H₉ 109-110 519 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅ (CH₂)₂OCH₃ — 520 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅ CH₂OC₂H₅ — 521 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₃H₇ C₃H₇ 115-120 522 CH₃ O H CH₃ CH₃ H CH₃ C₃H₇ C₃H₇ — 523 CH₃ CH₂ H Cl Cl H H C₃H₇ C₃H₇ 99-101 524 CH₃ CH₂ H CH₃ OCH₂ H H C₃H₇ C₃H₇ oil 525 CH₃ CH₂ H OCH₂ CH₂ H CH₃ C₃H₇ C₃H₇ 109-111 526 CH₃ CH₂ H CH₃ Cl H H C₃H₇ C₃H₇ oil 527 CH₃ CH₂ H CH₃ CH₃ CH₃ H C₃H₇ C₃H₇ — 528 CH₃ CH₂ H Cl CF₃ H H C₃H₇ C₃H₇ oil 529 CH₃ CH₂ H Cl CF₃ H Cl C₃H₇ C₃H₇ — 530 CH₃ CH₂ H OCH₃ Cl H Cl C₃H₇ C₃H₇ 129-131 531 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃ (CH₃)₂CHCH₂ 77-85 532 CH₃ O H CH₃ CH₃ H CH₃ CH₃ (CH₃)₂CHCH₂ — 533 CH₃ CH₂ H Cl Cl H H CH₃ (CH₃)₂CHCH₂ — 534 CH₃ CH₂ H CH₃ OCH₃ H H CH₃ (CH₃)₂CHCH₂ — 535 CH₃ CH₂ H OCH₃ CH₂ H Cl CH₃ (CH₃)₂CHCH₂ — 536 CH₃ CH₂ H CH₃ Cl H H CH₃ (CH₃)₂CHCH₂ — 537 CH₃ CH₂ H CH₃ CH₃ CH₃ H CH₃ (CH₃)₂CHCH₂ — 538 CH₃ CH₂ H Cl CF₃ H H C₂H₅ (CH₃)₂CH oil 539 CH₃ CH₂ H Cl CF₃ H Cl CH₃ (CH₃)₂CHCH₂ — 540 CH₃ CH₂ H OCH₃ Cl H Cl CH₃ (CH₃)₂CHCH₂ — 541 CH₃ CH₂ H CH₃ CH₂ H CH₃ CH₃ c-C₃H₅ 118-127 542 CH₃ O H CH₃ CH₃ H CH₃ CH₃ c-C₃H₅ — 543 CH₃ CH₂ H Cl Cl H H CH₃ c-C₃H₅ oil 544 CH₃ CH₂ H CH₃ OCH₃ H H CH₃ c-C₃H₅ oil 545 CH₃ CH₂ H OCH₃ OCH₃ H CH₃ CH₃ c-C₃H₅ — 546 CH₃ CH₂ H CH₃ Cl H H CH₃ c-C₃H₅ — 547 CH₃ CH₂ H CH₃ CH₃ CH₃ H CH₃ c-C₃H₅ — 548 CH₃ CH₂ H Cl CF₃ H H CH₃ c-C₃H₅ oil 549 CH₃ CH₂ H Cl CF₃ H Cl CH₃ c-C₃H₅ — 550 CH₃ CH₂ H OCH₃ Cl H Cl CH₃ c-C₃H₅ — 551 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃ CH₃ oil 552 CH₃ O H CH₃ CH₃ H CH₃ CH₃ CH₃ — 553 CH₃ CH₂ H Cl Cl H H CH₃ CH₃ — 554 CH₃ CH₂ H CH₃ OCH₃ H H CH₃ CH₃ — 555 CH₃ CH₂ H OCH₃ CH₃ H CH₃ CH₃ CH₃ — 556 CH₃ CH₂ H CH₃ Cl H H CH₃ CH₃ — 557 CH₃ CH₂ H CH₃ CH₃ CH₃ H CH₃ CH₃ — 558 CH₃ CH₂ H Cl CF₃ H H CH₃ C₄H₉ oil 559 CH₃ CH₂ H Cl CF₃ H Cl CH₃ CH₃ — 560 CH₃ CH₂ H OCH₃ Cl H Cl CH₃ CH₃ — 561 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₅H₁₁ 102-103 562 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₅H₁₁ — 563 CH₃ CH₂ H Cl Cl H H C₂H₅ C₅H₁₁ — 564 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ C₄H₉ oil 565 CH₃ CH₂ H OCH₃ CH₃ H CH₃ C₂H₅ C₅H₁₁ — 566 CH₃ CH₂ H CH₃ Cl H H C₂H₅ C₅H₁₁ — 567 CH₃ CH₂ H CH₃ CH₃ CH₃ H C₂H₅ C₅H₁₁ — 568 CH₃ CH₂ H Cl CF₃ H H C₂H₅ C₅H₁₁ — 569 CH₃ CH₂ H Cl CF₃ H Cl C₂H₅ C₅H₁₁ — 570 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅ C₅H₁₁ — 571 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅O(CH₂)₂ oil 572 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅O(CH₂)₂ — 573 CH₃ CH₂ H Cl Cl H H C₂H₅ C₂H₅O(CH₂)₂ — 574 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ C₂H₅O(CH₂)₂ — 575 CH₃ CH₂ H OCh₃ CH₃ H CH₃ C₂H₅ C₂H₅O(CH₂)₂ — 576 CH₃ CH₂ H CH₃ Cl H H C₂H₅ C₂H₅O(CH₂)₂ — 577 CH₃ CH₂ H CH₃ CH₃ CH₃ H C₂H₅ C₂H₅O(CH₂)₂ — 578 CH₃ CH₂ H Cl CF₃ H H C₂H₅ C₂H₅O(CH₂)₂ — 579 CH₃ CH₂ H Cl CF₃ H Cl C₂H₅ C₂H₅O(CH₂)₂ — 580 CH₃ CH₂ H OCH₂ Cl H Cl C₂H₅ C₂H₅O(CH₂)₂ — 581 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅OCH₂ oil 582 CH₃ O H CH₃ CH₃ H CH₃ C₂H₅ C₂H₅OCH₂ — 583 CH₃ CH₂ H Cl Cl H H C₂H₅ C₂H₅OCH₂ — 584 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ C₂H₅OCH₂ — 585 CH₃ CH₂ H OCH₃ CH₃ H CH₃ C₂H₅ C₂H₅OCH₂ — 586 CH₃ CH₂ H CH₃ Cl H H C₂H₅ C₂H₅OCH₂ — 587 CH₃ CH₂ H CH₃ CH₃ CH₃ H C₂H₅ C₂H₅OCH₂ — 588 CH₃ CH₂ H Cl CF₃ H H C₂H₅ C₂H₅OCH₂ — 589 CH₃ CH₂ H Cl CF₃ H Cl C₂H₅ C₂H₅OCH₂ — 590 CH₃ CH₂ H OCH₃ Cl H Cl C₂H₅ C₂H₅OCH₂ — 591 CH₃ CH₂ H CH₃ CH₃ H CH₃ H c-C₃H₅CH(OMe) oil (CH₂)₂ 592 CH₃ O H CH₃ CH₃ H CH₃ H c-C₃H₅CH(OMe) — (CH₂)₂ 593 CH₃ CH₂ H Cl Cl H H H c-C₃H₅CH(OMe) — (CH₂)₂ 594 CH₃ CH₂ H CH₃ OCH₃ H H H c-C₃H₅CH(OMe) — (CH₂)₂ 595 CH₃ CH₂ H OCH₂ CH₃ H CH₃ H c-C₃H₅CH(OMe) — (CH₂)₂ 596 CH₃ CH₂ H CH₃ Cl H H H c-C₃H₅CH(OMe) — (CH₂)₂ 597 CH₃ CH₂ H CH₃ CH₃ CH₃ H H c-C₃H₅CH(OMe) — (CH₂)₂ 598 CH₃ CH₂ H Cl CF₃ H H H c-C₃H₅CH(OMe) — (CH₂)₂ 599 CH₃ CH₂ H Cl CF₃ H Cl H c-C₃H₅CH(OMe) — (CH₂)₂ 600 CH₃ CH₂ H OCH₃ Cl H Cl H c-C₃H₅CH(OMe) — (CH₂)₂ 601 CH₃ CH₂ CH₂ Cl Cl H H C₂H₅ C₂H₅ — 602 CH₃ CH₂ CH₂ Cl Cl H H c-C₃H₅ C₄H₉ 603 CH₃ CH₂ CH₂ Cl Cl H H c-C₃H₅ c-C₃H₅ 155-156 604 CH₃ CH₂ CH₂ Cl Cl H H H C₄H₉ — 605 CH₃ CH₂ CH₂ Cl Cl H H C₂H₅ C₄H₉ — 606 CH₃ CH₂ CH₂ Cl Cl H H H C₆H₅ — 607 CH₃ CH₂ CH₂ Cl Cl H H C₂H₅ (CH₂)₂OCH₃ — 608 CH₃ CH₂ CH₂ Cl Cl H H CH₃ C₄H₉ — 609 CH₃ CH₂ CH₂ Cl Cl H H C₃H₇ C₃H₇ — 610 CH₃ CH₂ CH₂ Cl Cl H H C₂H₅ C₃H₇ — 611 CH₃ CH₂ CH₂ OCH₃ CH₃ H CH₃ C₂H₅ C₂H₅ — 612 CH₃ CH₂ CH₂ OCH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 613 CH₃ CH₂ CH₂ OCH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 614 CH₃ CH₂ CH₂ OCH₃ CH₃ H CH₃ H C₄H₉ — 615 CH₃ CH₂ CH₂ OCH₃ CH₃ H CH₃ C₂H₅ C₄H₉ — 616 CH₃ CH₂ CH₂ OCH₂ CH₃ H CH₃ H C₆H₅ — 617 CH₃ CH₂ CH₂ OCH₂ CH₃ H CH₃ C₂H₅ (CH₂)₂OCH₃ — 618 CH₃ CH₂ CH₂ OCH₃ CH₃ H CH₃ CH₃ C₄H₉ — 619 CH₃ CH₂ CH₂ OCH₃ CH₃ H CH₃ C₃H₇ C₃H₇ — 620 CH₃ CH₂ CH₂ OCH₃ CH₃ H CH₃ C₂H₅ C₃H₇ — 621 CH₃ CH₂ CH₂ CH₃ OCH₃ H H C₂H₅ C₂H₅ — 622 CH₃ CH₂ CH₂ CH₃ OCH₃ H H c-C₃H₅ C₄H₉ — 623 CH₃ CH₂ CH₂ CH₃ OCH₃ H H c-C₃H₅ c-C₃H₅ — 624 CH₃ CH₂ CH₂ CH₃ OCH₃ H H H C₄H₉ — 625 CH₃ CH₂ CH₂ CH₃ OCH₃ H H C₂H₅ C₄H₉ — 626 CH₃ CH₂ CH₂ CH₃ OCH₃ H H H C₆H₅ — 627 CH₃ CH₂ CH₂ CH₃ OCH₃ H H C₂H₅ (CH₂)₂OCH₃ — 628 CH₃ CH₂ CH₂ CH₃ OCH₃ H H CH₃ C₄H₉ — 629 CH₃ CH₂ CH₂ CH₃ OCH₃ H H C₃H₇ C₃H₇ — 630 CH₃ CH₂ CH₂ CH₃ OCH₃ H H C₂H₅ C₃H₇ — 631 CH₃ CH₂ CH₂ CH₃ Cl H H C₂H₅ C₂H₅ — 632 CH₃ CH₂ CH₂ CH₃ Cl H H c-C₃H₅ C₄H₉ — 633 CH₃ CH₂ CH₂ CH₃ Cl H H c-C₃H₅ c-C₃H₅ — 634 CH₃ CH₂ CH₂ CH₃ Cl H H H C₄H₉ — 635 CH₂ CH₂ CH₂ CH₃ Cl H H C₂H₅ C₄H₉ — 636 CH₃ CH₂ CH₃ CH₃ Cl H H H C₆H₅ — 637 CH₃ CH₂ CH₃ CH₃ Cl H H C₂H₅ (CH₂)₂OCH₃ — 638 CH₃ CH₂ CH₃ CH₃ Cl H H CH₃ C₄H₉ — 639 CH₃ CH₂ CH₃ CH₃ Cl H H C₃H₇ C₃H₇ — 640 CH₃ CH₂ CH₃ CH₃ Cl H H C₂H₅ C₃H₇ — 641 CH₃ CH₂ CH₃ Cl CF₃ H H C₂H₅ C₂H₅ — 642 CH₃ CH₂ CH₃ Cl CF₃ H H c-C₃H₅ C₄H₉ — 643 CH₃ CH₂ CH₃ Cl CF₃ H H c-C₃H₅ c-C₃H₅ — 644 CH₃ CH₂ CH₃ Cl CF₃ H H H C₄H₉ — 645 CH₃ CH₂ CH₃ Cl CF₃ H H C₂H₅ C₄H₉ — 646 CH₃ CH₂ CH₃ Cl CF₃ H H H C₆H₅ — 647 CH₃ CH₂ CH₃ Cl CF₃ H H C₂H₅ (CH₂)₂OCH₃ — 648 CH₃ CH₂ CH₃ Cl CF₃ H H CH₃ C₄H₉ — 649 CH₃ CH₂ CH₃ Cl CF₃ H H C₃H₇ C₃H₇ — 650 CH₃ CH₂ CH₃ Cl CF₃ H H C₂H₅ C₃H₇ — 651 CH₃ CH₂ CH₃ Cl CF₃ H Cl C₂H₅ C₂H₅ — 652 CH₃ CH₂ CH₃ Cl CF₃ H Cl c-C₃H₅ C₄H₉ — 653 CH₃ CH₂ CH₃ Cl CF₃ H Cl c-C₃H₅ c-C₃H₅ — 654 CH₃ CH₂ CH₃ Cl CF₃ H Cl H C₄H₉ — 655 CH₃ CH₂ CH₃ Cl CF₃ H Cl C₂H₅ C₄H₉ — 656 CH₃ CH₂ CH₃ Cl CF₃ H Cl H C₆H₅ — 657 CH₃ CH₂ CH₃ Cl CF₃ H Cl C₂H₅ (CH₂)₂OCH₃ — 658 CH₃ CH₂ CH₃ Cl CF₃ H Cl CH₃ C₄H₉ — 659 CH₃ CH₂ CH₃ Cl CF₃ H Cl C₃H₇ C₃H₇ — 660 CH₃ CH₂ CH₃ Cl CF₃ H Cl C₂H₅ C₃H₇ — 661 CH₃ CH₂ CH₃ OCH₃ Cl H Cl C₂H₅ C₂H₅ — 662 CH₃ CH₂ CH₃ OCH₃ Cl H Cl c-C₃H₅ C₄H₉ — 663 CH₃ CH₂ CH₃ OCH₃ Cl H Cl c-C₃H₅ c-C₃H₅ — 664 CH₃ CH₂ CH₃ OCH₃ Cl H Cl H C₄H₉ — 665 CH₃ CH₂ CH₃ OCH₃ Cl H Cl C₂H₅ C₄H₉ — 666 CH₃ CH₂ CH₃ OCH₃ Cl H Cl H C₆H₅ — 667 CH₃ CH₂ CH₃ OCH₃ Cl H Cl C₂H₅ (CH₂)₂OCH₃ — 668 CH₃ CH₂ CH₃ OCH₃ Cl H Cl CH₃ C₄H₉ — 669 CH₃ CH₂ CH₃ OCH₃ Cl H Cl C₃H₇ C₃H₇ — 670 CH₃ CH₂ CH₃ OCH₃ Cl H Cl C₂H₅ C₃H₇ — 671 CH₃ CH₂ CH₃ CH₃ CH₃ H H C₃H₅ C₂H₅ — 672 CH₃ CH₂ CH₃ CH₃ CH₃ H H c-C₃H₅ C₄H₉ — 673 CH₃ CH₂ CH₃ CH₃ CH₃ H H c-C₃H₅ c-C₃H₅ — 674 CH₃ CH₂ CH₃ CH₃ CH₃ H H H C₄H₉ — 675 CH₃ CH₂ CH₃ CH₃ CH₃ H H C₂H₅ C₄H₉ — 676 CH₃ CH₂ CH₃ CH₃ CH₃ H H H C₆H₅ — 677 CH₃ CH₂ CH₃ CH₃ CH₃ H H C₂H₅ (CH₂)₂OCH₃ — 676 CH₃ CH₂ CH₃ CH₃ CH₃ H H CH₃ C₄H₉ — 679 CH₃ CH₂ CH₃ CH₃ CH₃ H H C₃H₇ C₃H₉ — 680 CH₃ CH₂ CH₃ CH₃ CH₃ H H C₂H₅ C₃H₉ — 661 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ C₄H₉ — 682 CH₃ CH₂ H OCH₃ CH₃ H CH₃ C₂H₅ C₄H₉ 107-109 683 CH₃ CH₂ H Cl CF₃ H Cl C₂H₅ C₄H₉ — 684 CH₃ CH₂ H CH₃ CH₃ CH₃ H C₂H₅ C₄H₉ — 685 CH₃ CH₂ H CH₃ OCH₃ H H c-C₃H₅ c-C₃H₉ 101-103 686 CH₃ CH₂ H OCH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₉ 167-168 687 CH₃ CH₂ H Cl CF₃ H Cl c-C₃H₅ c-C₃H₉ — 688 CH₃ CH₂ H CH₃ CH₃ CH₃ H c-C₃H₅ c-C₃H₉ 119-121 689 CH₃ CH₂ H CH₃ OCH₃ H H H C₆H₅ 108-109 690 CH₃ CH₂ H OCH₃ CH₃ H CH₃ H C₆H₅ oil 691 CH₃ CH₂ H Cl CF₃ H Cl H C₆H₅ — 692 CH₃ CH₂ H CH₃ CH₃ CH₃ H H C₆H₅ oil 693 CH₃ CH₂ H CH₃ OCH₃ H H c-C₃H₉ C₄H₉ oil 694 CH₃ CH₂ H OCH₃ CH₃ H CH₃ c-C₃H₉ C₄H₉ — 695 CH₃ CH₂ H Cl CF₃ H Cl c-C₃H₉ C₄H₉ — 696 CH₃ CH₂ H CH₃ CH₃ CH₃ H c-C₃H₉ C₄H₉ — 697 CH₃ CH₂ H CH₃ OCH₃ H H CH₃ C₄H₉ oil 698 CH₃ CH₂ H OCH₃ CH₃ H CH₃ CH₃ C₄H₉ — 699 CH₃ CH₂ H Cl CF₃ H Cl CH₃ C₄H₉ — 700 CH₃ CH₂ H CH₃ CH₃ CH₃ H CH₃ C₄H₉ — 701 CH₃ O H CH₃ OCH₃ H H C₂H₅ C₄H₉ — 702 CH₃ O H OCH₃ CH₃ H CH₃ C₂H₅ C₄H₉ — 703 CH₃ O H Cl CF₃ H Cl C₂H₅ C₄H₉ — 704 CH₃ O H CH₃ CH₃ CH₃ H C₂H₅ C₄H₉ — 705 CH₃ O H CH₃ OCH₃ H H c-C₃H₅ c-C₃H₅ — 706 CH₃ O H OCH₃ CH₃ H CH₃ c-C₃H₅ c-C₃H₅ — 707 CH₃ O H Cl CF₃ H Cl c-C₃H₅ c-C₃H₅ — 708 CH₃ O H CH₃ CH₃ CH₃ H c-C₃H₅ c-C₃H₅ — 709 CH₃ O H CH₃ OCH₃ H H H C₆H₅ — 710 CH₃ O H OCH₃ CH₃ H CH₃ H C₆H₅ — 711 CH₃ O H Cl CF₃ H Cl H C₆H₅ — 712 CH₃ O H CH₃ CH₃ CH₃ H H C₆H₅ — 713 CH₃ O H CH₃ OCH₃ H H c-C₃H₅ C₄H₉ — 714 CH₃ O H OCH₃ CH₃ H CH₃ c-C₃H₅ C₄H₉ — 715 CH₃ O H Cl CF₃ H Cl c-C₃H₅ C₄H₉ — 716 CH₃ O H CH₃ CH₃ CH₃ H c-C₃H₅ C₄H₉ — 717 CH₃ O H CH₃ OCH₃ H H CH₃ C₄H₉ — 718 CH₃ O H OCH₃ CH₃ H CH₃ CH₃ C₄H₉ — 719 CH₃ O H Cl CF₃ H Cl CH₃ C₄H₉ — 720 CH₃ O H CH₃ CH₃ CH₃ H CH₃ C₄H₉ — 721 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH(CH₃)₂ 146-147 722 CH₃ CH₂ H Cl Cl H H C₂H₅ CH(CH₃)₂ — 723 CH₃ CH₂ H Cl CH₃ H H C₂H₅ CH(CH₃)₂ — 724 CH₃ CH₂ H Cl OCH₂ H H C₂H₅ CH(CH₃)₂ oil 725 CH₃ CH₂ H CH₃ OCH₂ H H C₂H₅ CH(CH₃)₂ oil 726 CH₃ CH₂ H Cl CF₃ H H C₂H₅ CH(CH₃)₂ — 727 CH₃ CH₂ H CF₃ Cl H H C₂H₅ CH(CH₃)₂ oil 728 CH₃ CH₂ H CH₃ Cl H H C₂H₅ CH(CH₃)₂ — 729 CH₃ CH₂ H CF₃ CF₃ H H C₂H₅ CH(CH₃)₂ — 730 CH₃ CH₂ H Cl CN H H C₂H₅ CH(CH₃)₂ — 731 CH₃ CH₂ H Cl Cl F H C₂H₅ CH(CH₃)₂ — 732 CH₃ CH₂ H Cl Cl Cl H C₂H₅ CH(CH₃)₂ — 733 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅ CH(CH₃)₂ — 734 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ CH(CH₃)₂ — 735 CH₃ CH₂ H Cl CH₃ F H C₂H₅ CH(CH₃)₂ — 736 CH₃ CH₂ H Cl CF₃ Cl H C₂H₅ CH(CH₃)₂ — 737 CH₃ CH₂ H Cl CF₃ F H C₂H₅ CH(CH₃)₂ — 738 CH₃ CH₂ H Cl OCH₃ Cl H C₂H₅ CH(CH₃)₂ — 739 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ CH(CH₃)₂ — 740 CH₃ CH₂ H Cl OCH₃ CH₃ H C₂H₅ CH(CH₃)₂ — 741 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ CH(CH₃)₂ — 742 CH₃ CH₂ H Cl H Cl H C₂H₅ CH(CH₃)₂ — 743 CH₃ CH₂ H Cl Cl OCH₃ H C₂H₅ CH(CH₃)₂ — 744 CH₃ CH₂ H Cl CH₃ OCH₃ H C₂H₅ CH(CH₃)₂ — 745 CH₃ CH₂ H CH₃ Cl OCH₃ H C₂H₅ CH(CH₃)₂ — 746 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₂H₅ CH(CH₃)₂ — 747 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃H₇ c-C₃H₅ 140-143 748 CH₃ CH₂ H Cl Cl H H C₃H₇ c-C₃H₅ 107-108 (A) 79-82 (C) 749 CH₃ CH₂ H Cl CH₃ H H C₃H₇ c-C₃H₅ 106-108 750 CH₃ CH₂ H Cl OCH₃ H H C₃H₇ c-C₃H₅ oil 751 CH₃ CH₂ H CH₃ OCH₃ H H C₃H₇ c-C₃H₅ oil 752 CH₃ CH₃ H Cl CF₃ H H C₃H₇ c-C₃H₅ 108-109 753 CH₃ CH₂ H CF₃ Cl H H C₃H₇ c-C₃H₅ oil (A) 95-97 (C) 754 CH₃ CH₂ H CH₃ Cl H H C₃H₇ c-C₃H₅ 87-88 755 CH₃ CH₂ H CF₃ CF₃ H H C₃H₇ c-C₃H₅ — 756 CH₃ CH₂ H Cl CN H H C₃H₇ c-C₃H₅ — 757 CH₃ CH₂ H Cl Cl F H C₃H₇ c-C₃H₅ — 758 CH₃ CH₂ H Cl Cl Cl H C₃H₇ c-C₃H₅ — 759 CH₃ CH₂ H CH₃ OCH₃ F H C₃H₇ c-C₃H₅ — 760 CH₃ CH₂ H CH₃ OCH₃ Cl H C₃H₇ c-C₃H₅ — 761 CH₃ CH₂ H Cl CH₃ F H C₃H₇ c-C₃H₅ — 762 CH₃ CH₂ H Cl CF₃ Cl H C₃H₇ c-C₃H₅ — 763 CH₃ CH₂ H Cl CF₃ F H C₃H₇ c-C₃H₅ — 764 CH₃ CH₂ H Cl OCH₃ Cl H C₃H₇ c-C₃H₅ — 765 CH₃ CH₂ H Cl OCH₃ F H C₃H₇ c-C₃H₅ — 766 CH₃ CH₂ H Cl OCH₃ CH₃ H C₃H₇ c-C₃H₅ — 767 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₃H₇ c-C₃H₅ oil 768 CH₃ CH₂ H Cl H Cl H C₃H₇ c-C₃H₅ — 769 CH₃ CH₂ H Cl Cl OCH₃ H C₃H₇ c-C₃H₅ — 770 CH₃ CH₂ H Cl CH₃ OCH₃ H C₃H₇ c-C₃H₅ — 771 CH₃ CH₂ H CH₃ Cl OCH₃ H C₃H₇ c-C₃H₅ — 772 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₃H₇ c-C₃H₅ — 773 CH₃ CH₂ H CH₃ CH₃ H CH₃ CH₃ CH₂Cl 109-110 774 CH₃ CH₂ H Cl Cl H H C₂H₅ C₃H₇ — 775 CH₃ CH₂ H Cl CH₃ H H C₂H₅ C₃H₇ — 776 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ C₃H₇ oil 777 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ C₃H₇ oil 778 CH₃ CH₂ H Cl CF₃ H H C₂H₅ C₃H₇ oil 779 CH₃ CH₂ H CF₃ Cl H H C₂H₅ C₃H₇ oil 780 CH₃ CH₂ H CH₃ Cl H H C₂H₅ C₃H₇ — 781 CH₃ CH₂ H CF₃ CF₃ H H C₂H₅ C₃H₇ — 782 CH₃ CH₂ H Cl CN H H C₂H₅ C₃H₇ — 783 CH₃ CH₂ H Cl Cl F H C₂H₅ C₃H₇ — 784 CH₃ CH₂ H Cl Cl Cl H C₂H₅ C₃H₇ — 785 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅ C₃H₇ — 786 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ C₃H₇ — 787 CH₃ CH₂ H Cl CH₃ F H C₂H₅ C₃H₇ — 788 CH₃ CH₂ H Cl CF₃ Cl H C₂H₅ C₃H₇ — 789 CH₃ CH₂ H Cl CF₃ F H C₂H₅ C₃H₇ — 790 CH₃ CH₂ H Cl OCH₃ Cl H C₂H₅ C₃H₇ — 791 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ C₃H₇ — 792 CH₃ CH₂ H Cl OCH₃ CH₃ H C₂H₅ C₃H₇ — 793 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ C₃H₇ oil 794 CH₃ CH₂ H Cl H Cl H C₂H₅ C₃H₇ — 795 CH₃ CH₂ H Cl Cl OCH₃ H C₂H₅ C₃H₇ — 796 CH₃ CH₂ H Cl CH₃ OCH₃ H C₂H₅ C₃H₇ — 797 CH₃ CH₂ H CH₃ Cl OCH₃ H C₂H₅ C₃H₇ — 798 CH₃ CH₂ H CH₃ CH₂ OCH₃ H C₂H₅ C₃H₇ — 799 CH₃ CH₂ H CH₃ CH₂ CH₃ H C₂H₅ C₃H₇ oil 800 CH₃ CH₂ H CF₃ Cl H H H 4-CH₃O—C₆H₄ 138-139 801 CH₃ CH₂ H CF₃ Cl H H c-C₃H₅ c-C₃H₅ 138-139 802 CH₃ CH₂ H CF₃ Cl H H C₂H₅ c-C₃H₅ oil (A) 122-125 (C) 803 CH₃ CH₂ H CF₃ Cl H H CH₃ c-C₃H₅ oil 804 CH₃ CH₂ H CF₃ Cl H H CH₃ C₃H₇ oil 805 CH₃ CH₂ H CF₃ Cl H H CH₃ C₄H₉ oil 806 CH₃ CH₂ H CF₃ Cl H H CH₃ C₅H₁₁ — 807 CH₃ CH₂ H CF₃ Cl H H C₂H₅ C₄H₉ oil 808 CH₃ CH₂ H CF₃ Cl H H C₃H₇ C₃H₇ oil 809 CH₃ CH₂ H CF₃ Cl H H C₂H₅ C₂H₅ oil 810 CH₃ CH₂ H Cl CN H H H 4-CH₃O—C₆H₄ — 811 CH₃ CH₂ H Cl CN H H c-C₃H₅ c-C₃H₅ 180-182 812 CH₃ CH₂ H Cl CN H H C₂H₅ c-C₃H₅ — 813 CH₃ CH₂ H Cl CN H H CH₃ c-C₃H₅ — 814 CH₃ CH₂ H Cl CN H H CH₃ C₃H₇ — 815 CH₃ CH₂ H Cl CN H H CH₃ C₄H₉ — 816 CH₃ CH₂ H Cl CN H H CH₃ C₅H₁₁ — 817 CH₃ CH₂ H Cl CN H H C₂H₅ C₄H₉ — 818 CH₃ CH₂ H Cl CN H H C₃H₇ C₃H₇ — 819 CH₃ CH₂ H Cl CN H H C₂H₅ C₂H₅ — 820 CH₃ CH₂ H CF₃ CF₃ H H H 4-CH₃O—C₆H₄ — 821 CH₃ CH₂ H CF₃ CF₃ H H c-C₃H₅ c-C₃H₅ 149-150 822 CH₃ CH₂ H CF₃ CF₃ H H C₂H₅ c-C₃H₅ — 823 CH₃ CH₂ H CF₃ CF₃ H H CH₃ c-C₃H₅ — 824 CH₃ CH₂ H CF₃ CF₃ H H CH₃ C₃H₇ oil 825 CH₃ CH₂ H CF₃ CF₃ H H CH₃ C₄H₉ — 826 CH₃ CH₂ H CF₃ CF₃ H H CH₃ C₅H₁₁ — 827 CH₃ CH₂ H CF₃ CF₃ H H C₂H₅ C₄H₉ — 828 CH₃ CH₂ H CF₃ CF₃ H H C₃H₅ C₃H₇ — 829 CH₃ CH₂ H CF₃ CF₃ H H C₂H₅ C₂H₅ — 830 CH₃ CH₂ H Cl OCH₃ H H H 4-CH₃O—C₆H₄ 58-60 831 CH₃ CH₂ H Cl OCH₃ H H c-C₃H₅ c-C₃H₅ 139-140 832 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ c-C₃H₅ oil 833 CH₃ CH₂ H Cl OCH₃ H H H c-C₃H₅ oil 834 CH₃ CH₂ H Cl OCH₃ H H CH₃ C₃H₇ oil 835 CH₃ CH₂ H Cl OCH₃ H H CH₃ C₄H₉ oil 836 CH₃ CH₂ H Cl OCH₃ H H CH₃ C₅H₁₁ oil 837 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ C₄H₉ oil 838 CH₃ CH₂ H Cl OCH₃ H H C₃H₇ C₃H₇ oil 839 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ C₂H₅ oil 840 CH₃ CH₂ H Cl OCH₃ F H H 4-CH₃O—C₆H₄ — 841 CH₃ CH₂ H Cl Cl F H c-C₃H₅ c-C₃H₅ 148-149 842 CH₃ CH₂ H Cl Cl F H C₂H₅ c-C₃H₅ — 843 CH₃ CH₂ H Cl Cl F H CH₃ c-C₃H₅ — 844 CH₃ CH₂ H Cl Cl F H CH₃ C₃H₇ — 845 CH₃ CH₂ H Cl Cl F H CH₃ C₄H₉ — 846 CH₃ CH₂ H Cl Cl F H CH₃ C₅H₁₁ — 847 CH₃ CH₂ H Cl Cl F H C₂H₅ C₄H₉ — 848 CH₃ CH₂ H Cl Cl F H C₃H₇ C₃H₇ — 849 CH₃ CH₂ H Cl Cl F H C₂H₅ C₂H₅ — 850 CH₃ CH₂ H Cl Cl Cl H H 4-CH₃O—C₆H₄ — 851 CH₃ CH₂ H Cl Cl Cl H c-C₃H₅ c-C₃H₅ — 852 CH₃ CH₂ H Cl Cl Cl H C₂H₅ c-C₃H₅ — 853 CH₃ CH₂ H Cl Cl Cl H CH₃ c-C₃H₅ — 854 CH₃ CH₂ H Cl Cl Cl H CH₃ C₃H₇ — 855 CH₃ CH₂ H Cl Cl Cl H CH₃ C₄H₉ — 856 CH₃ CH₂ H Cl Cl Cl H CH₃ C₅H₁₁ — 857 CH₃ CH₂ H Cl Cl Cl H C₂H₅ C₄H₉ — 858 CH₃ CH₂ H Cl Cl Cl H C₃H₇ C₃H₇ — 859 CH₃ CH₂ H Cl Cl Cl H C₂H₅ C₂H₅ — 860 CH₃ CH₂ H CH₃ OCH₃ F H H 4-CH₂O—C₆H₅ — 861 CH₃ CH₂ H CH₃ OCH₃ F H c-C₃H₅ c-C₃H₅ 128-129 862 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅ c-C₃H₅ — 863 CH₃ CH₂ H CH₃ OCH₃ F H CH₃ c-C₃H₅ — 864 CH₃ CH₂ H CH₃ OCH₃ F H CH₃ C₃H₇ — 865 CH₃ CH₂ H CH₃ OCH₃ F H CH₃ C₄H₉ — 866 CH₃ CH₂ H CH₃ OCH₃ F H CH₃ C₅H₁₁ — 867 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅ C₄H₉ — 868 CH₃ CH₂ H CH₃ OCH₃ F H C₃H₅ C₃H₇ — 869 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅ C₂H₅ — 870 CH₃ CH₂ H CH₃ OCH₃ Cl H H 4-CH₃O—C₆H₄ oil 871 CH₃ CH₂ H CH₃ OCH₃ Cl H c-C₃H₅ c-C₃H₅ 179-181 872 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ c-C₃H₅ — 873 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ c-C₃H₅ — 874 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ C₃H₇ — 875 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ C₄H₉ — 876 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ C₅H₁₁ — 877 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ C₄H₉ — 878 CH₃ CH₂ H CH₃ OCH₃ Cl H C₃H₇ C₃H₇ — 879 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ C₂H₅ — 880 CH₃ CH₂ H CH₃ CH₃ F H H 4-CH₃O—C₆H₄ — 881 CH₃ CH₂ H Cl CH₃ F H c-C₃H₅ c-C₃H₅ 130-131 882 CH₃ CH₂ H Cl CH₃ F H C₂H₅ c-C₃H₅ — 883 CH₃ CH₂ H Cl CH₃ F H CH₃ c-C₃H₅ — 884 CH₃ CH₂ H Cl CH₃ F H CH₃ C₃H₇ — 885 CH₃ CH₂ H Cl CH₃ F H CH₃ C₄H₉ — 886 CH₃ CH₂ H Cl CH₃ F H CH₃ C₅H₁₁ — 887 CH₃ CH₂ H Cl CH₃ F H C₂H₅ C₄H₉ — 888 CH₃ CH₂ H Cl CH₃ F H C₃H₇ C₃H₇ — 889 CH₃ CH₂ H Cl CH₃ F H C₂H₅ C₂H₅ — 890 CH₃ CH₂ H Cl CF₃ Cl H H 4-CH₃O—C₆H₄ — 891 CH₃ CH₂ H Cl CF₃ Cl H c-C₃H₅ c-C₃H₅ — 892 CH₃ CH₂ H Cl CF₃ Cl H C₂H₅ c-C₃H₅ — 893 CH₃ CH₂ H Cl CF₃ Cl H CH₃ c-C₃H₅ — 894 CH₃ CH₂ H Cl CF₃ Cl H CH₃ C₃H₇ — 895 CH₃ CH₂ H Cl CF₃ Cl H CH₃ C₄H₉ — 896 CH₃ CH₂ H Cl CF₃ Cl H CH₃ C₅H₁₁ — 897 CH₃ CH₂ H Cl CF₃ Cl H C₂H₅ C₄H₉ — 898 CH₃ CH₂ H Cl CF₃ Cl H C₃H₇ C₃H₇ — 899 CH₃ CH₂ H Cl CF₃ Cl H C₂H₅ C₂H₅ — 900 CH₃ CH₂ H CH₃ OCH₃ H H H C₄H₉ oil 901 CH₃ CH₂ H CH₃ OCH₃ H H C₂H₅ C₂H₅ 69-73 902 CH₃ CH₂ H Cl CH₃ H H C₃H₇ C₃H₇ oil 903 CH₃ CH₂ H Cl CF₃ F H H 4-CH₃O—C₆H₄ — 904 CH₃ CH₂ H Cl CF₃ F H c-C₃H₅ c-C₃H₅ — 905 CH₃ CH₂ H Cl CF₃ F H C₂H₅ c-C₃H₅ — 906 CH₃ CH₂ H Cl CF₃ F H CH₃ c-C₃H₅ — 907 CH₃ CH₂ H Cl CF₃ F H CH₃ C₃H₇ — 908 CH₃ CH₂ H Cl CF₃ F H CH₃ C₄H₉ — 909 CH₃ CH₂ H Cl CF₃ F H CH₃ C₅H₁₁ — 910 CH₃ CH₂ H Cl CF₃ F H C₂H₅ C₄H₉ — 911 CH₃ CH₂ H Cl CF₃ F H C₃H₇ C₃H₅ — 912 CH₃ CH₂ H Cl CF₃ F H C₂H₅ C₂H₅ — 913 CH₃ CH₂ H Cl OCH₃ Cl H H 4-CH₃O—C₆H₄ — 914 CH₃ CH₂ H Cl OCH₃ Cl H c-C₃H₅ c-C₃H₅ oil 915 CH₂ CH₂ H Cl OCH₃ Cl H C₂H₅ c-C₃H₅ — 916 CH₃ CH₂ H Cl OCH₃ Cl H CH₃ c-C₃H₅ — 917 CH₃ CH₂ H Cl OCH₃ Cl H CH₃ C₃H₇ — 916 CH₃ CH₂ H Cl OCH₃ Cl H CH₃ C₄H₉ — 919 CH₃ CH₂ H Cl OCH₃ Cl H CH₃ C₅H₁₁ — 920 CH₃ CH₂ H Cl OCH₃ Cl H C₂H₅ C₄H₉ — 921 CH₃ CH₂ H Cl OCH₃ Cl H C₃H₇ C₃H₇ — 922 CH₃ CH₂ H Cl OCH₃ Cl H C₂H₅ C₂H₅ — 923 CH₃ CH₂ H Cl OCH₃ F H H 4-CH₃O—C₆H₄ — 924 CH₃ CH₂ H Cl OCH₃ F H c-C₃H₅ c-C₃H₅ — 925 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ c-C₃H₅ — 926 CH₃ CH₂ H Cl OCH₃ F H CH₃ c-C₃H₅ — 927 CH₃ CH₂ H Cl OCH₃ F H CH₃ C₃H₇ — 928 CH₃ CH₂ H Cl OCH₃ F H CH₃ C₄H₉ — 929 CH₃ CH₂ H Cl OCH₃ F H CH₃ C₅H₁₁ — 930 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ C₄H₉ — 931 CH₃ CH₂ H Cl OCH₃ F H C₃H₇ C₃H₇ — 932 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ C₂H₅ — 933 CH₃ CH₂ H Cl OCH₃ CH₃ H H 4-CH₃O—C₆H₄ — 934 CH₃ CH₂ H Cl OCH₃ CH₃ H c-C₃H₅ c-C₃H₅ 150-151 935 CH₃ CH₂ H Cl OCH₃ CH₃ H C₂H₅ c-C₃H₅ — 936 CH₃ CH₂ H Cl OCH₃ CH₃ H CH₃ c-C₃H₅ — 937 CH₃ CH₂ H Cl OCH₃ CH₃ H CH₃ C₃H₇ — 938 CH₃ CH₂ H Cl OCH₃ CH₃ H CH₃ C₄H₉ — 939 CH₃ CH₂ H Cl OCH₃ CH₃ H CH₃ C₅H₁₁ — 940 CH₃ CH₂ H Cl OCH₃ CH₃ H C₂H₅ C₄H₉ — 941 CH₃ CH₂ H Cl OCH₃ CH₃ H C₃H₇ C₃H₇ — 942 CH₃ CH₂ H Cl OCH₃ CH₃ H C₂H₅ C₂H₅ — 943 CH₃ CH₂ H CH₃ OCH₃ CH₃ H H 4-CH₃O—C₄H₄ — 944 CH₃ CH₂ H CH₃ OCH₃ CH₃ H c-C₃H₅ c-C₃H₅ 148-151 945 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ c-C₃H₅ oil 946 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ c-C₃H₅ — 947 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ C₃H₇ oil 948 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ C₄H₉ — 949 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₂ C₅H₁₁ — 950 CH₃ CH₂ H CH₃ OCH₃ CH₂ H C₂H₅ C₄H₉ — 951 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₃H₇ C₃H₇ oil 952 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ C₂H₅ oil 953 CH₃ CH₂ H Cl H Cl H H 4-CH₃O—C₆H₄ — 954 CH₃ CH₂ H Cl H Cl H c-C₃H₅ c-C₃H₅ 151-153 955 CH₃ CH₂ H Cl H Cl H C₂H₅ c-C₃H₅ — 956 CH₃ CH₂ H Cl H Cl H CH₃ c-C₃H₅ — 957 CH₃ CH₂ H Cl H Cl H CH₃ C₃H₇ — 958 CH₃ CH₂ H Cl H Cl H CH₃ C₄H₉ — 959 CH₃ CH₂ H Cl H Cl H CH₃ C₅H₁₁ — 960 CH₃ CH₂ H Cl H Cl H C₂H₅ C₄H₉ — 961 CH₃ CH₂ H Cl H Cl H C₃H₇ C₃H₇ — 962 CH₃ CH₂ H Cl H Cl H C₂H₅ C₂H₅ — 963 CH₃ CH₂ H Cl Cl OCH₃ H H 4-CH₃O—C₆H₄ — 964 CH₃ CH₂ H Cl Cl OCH₃ H c-C₃H₅ c-C₃H₅ — 965 CH₃ CH₂ H Cl Cl OCH₃ H C₂H₅ c-C₃H₅ — 966 CH₃ CH₂ H Cl Cl OCH₃ H CH₃ c-C₃H₅ — 967 CH₃ CH₂ H Cl Cl OCH₃ H CH₃ C₃H₇ — 968 CH₃ CH₂ H Cl Cl OCH₃ H CH₃ C₄H₉ — 969 CH₃ CH₂ H Cl Cl OCH₃ H CH₃ C₅H₁₁ — 970 CH₃ CH₂ H Cl Cl OCH₃ H C₂H₅ C₄H₉ — 971 CH₃ CH₂ H Cl Cl OCH₃ H C₃H₇ C₃H₇ — 972 CH₃ CH₂ H Cl Cl OCH₃ H C₂H₅ C₂H₅ — 973 CH₃ CH₂ H Cl CH₃ OCH₃ H H 4-CH₃O—C₆H₄ — 974 CH₃ CH₂ H Cl CH₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 975 CH₃ CH₂ H Cl CH₃ OCH₃ H C₂H₅ c-C₃H₅ — 976 CH₃ CH₂ H Cl CH₃ OCH₃ H CH₃ c-C₃H₅ — 977 CH₃ CH₂ H Cl CH₃ OCH₃ H CH₃ C₃H₇ — 978 CH₃ CH₂ H Cl CH₃ OCH₃ H CH₃ C₄H₉ — 979 CH₃ CH₂ H Cl CH₃ OCH₃ H CH₃ C₅H₁₁ — 980 CH₃ CH₂ H Cl CH₃ OCH₃ H C₂H₅ C₄H₉ — 981 CH₃ CH₂ H Cl CH₃ OCH₃ H C₃H₇ C₃H₇ — 982 CH₃ CH₂ H Cl CH₃ OCH₃ H C₂H₅ C₂H₅ — 983 CH₃ CH₂ H CH₃ Cl OCH₃ H H 4-CH₃O—C₆H₄ — 984 CH₃ CH₂ H CH₃ Cl OCH₃ H c-C₃H₅ c-C₃H₅ — 985 CH₃ CH₂ H CH₃ Cl OCH₃ H C₂H₅ c-C₃H₅ — 986 CH₃ CH₂ H CH₃ Cl OCH₃ H CH₃ c-C₃H₅ — 987 CH₃ CH₂ H CH₃ Cl OCH₃ H CH₃ C₃H₇ — 988 CH₃ CH₂ H CH₃ Cl OCH₃ H CH₃ C₄H₉ — 989 CH₃ CH₂ H CH₃ Cl OCH₃ H CH₃ C₅H₁₁ — 990 CH₃ CH₂ H CH₃ Cl OCH₃ H C₂H₅ C₄H₉ — 991 CH₃ CH₂ H CH₃ Cl OCH₃ H C₃H₇ C₃H₇ — 992 CH₃ CH₂ H CH₃ Cl OCH₂ H C₂H₅ C₂H₅ — 993 CH₃ CH₂ H CH₃ CH₃ OCH₃ H H 4-CH₃O—C₆H₄ — 994 CH₃ CH₂ H CH₃ CH₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 995 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₂H₅ c-C₃H₅ 996 CH₃ CH₂ H CH₃ CH₃ OCH₃ H CH₃ c-C₃H₅ — 997 CH₃ CH₂ H CH₃ CH₃ OCH₃ H CH₃ C₃H₇ — 998 CH₃ CH₂ H CH₃ CH₃ OCH₃ H CH₃ C₄H₉ — 999 CH₃ CH₂ H CH₃ CH₃ OCH₃ H CH₃ C₅H₁₁ — 1000 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₂H₅ C₄H₉ — 1001 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₃H₇ C₃H₇ — 1002 CH₃ CH₂ H CH₃ CH₃ OCH₃ H C₂H₅ C₂H₅ — 1003 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H H 4-CH₃O—C₆H₄ oil 1004 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H c-C₃H₅ c-C₃H₅ 138-140 1005 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H C₂H₅ c-C₃H₅ — 1006 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H CH₃ c-C₃H₅ — 1007 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H CH₃ C₃H₇ — 1008 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H CH₃ C₄H₉ — 1009 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H CH₃ C₅H₁₁ — 1010 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H C₂H₅ C₄H₉ — 1011 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H C₃H₇ C₃H₇ — 1012 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H C₂H₅ C₂H₅ oil 1013 CH₃ CH₂ H Cl OCH₃ OCH₃ H H 4-CH₃O—C₆H₅ — 1014 CH₃ CH₂ H Cl OCH₃ QCH₃ H c-C₃H₅ c-C₃H₅ — 1015 CH₃ CH₂ H Cl OCH₃ OCH₃ H C₂H₅ c-C₃H₅ — 1016 CH₃ CH₂ H Cl OCH₃ OCH₃ H CH₃ c-C₃H₅ — 1017 CH₃ CH₂ H Cl OCH₃ OCH₃ H CH₃ C₃H₇ — 1018 CH₃ CH₂ H Cl OCH₃ OCH₃ H CH₃ C₄H₉ — 1019 CH₃ CH₂ H Cl OCH₃ OCH₃ H CH₃ C₅H₁₁ — 1020 CH₃ CH₂ H Cl OCH₃ OCH₃ H C₂H₅ C₄H₉ — 1021 CH₃ CH₂ H Cl OCH₃ OCH₃ H C₃H₇ C₃H₇ — 1022 CH₃ CH₂ H Cl OCH₃ OCH₃ H C₂H₅ C₂H₅ — 1023 CH₃ CH₂ H Cl OCF₃ H H H 4-CH₃O—C₆H₄ oil 1024 CH₃ CH₂ H Cl OCF₃ H H c-C₃H₅ c-C₃H₅ 119-120 1025 CH₃ CH₂ H Cl OCF₃ H H C₂H₅ c-C₃H₅ 103-104 1026 CH₃ CH₂ H Cl OCF₃ H H CH₃ c-C₃H₅ — 1027 CH₃ CH₂ H Cl OCF₃ H H CH₃ C₃H₇ oil 1028 CH₃ CH₂ H Cl OCF₃ H H CH₃ C₄H₉ oil 1029 CH₃ CH₂ H Cl OCF₃ H H CH₃ C₅H₁₁ — 1030 CH₃ CH₂ H Cl OCF₃ H H C₂H₅ C₄H₉ — 1031 CH₃ CH₂ H Cl OCF₃ H H C₃H₇ C₃H₇ — 1032 CH₃ CH₂ H Cl OCF₃ H H C₂H₅ C₂H₅ oil 1033 CH₃ CH₂ H Cl SCF₃ H H H 4-CH₃O—C₄H₄ — 1034 CH₃ CH₂ H Cl SCF₃ H H c-C₃H₅ c-C₃H₅ — 1035 CH₃ CH₃ H Cl SCF₃ H H C₂H₅ c-C₃H₅ — 1036 CH₃ CH₂ H Cl SCF₃ H H CH₃ c-C₃H₅ — 1037 CH₃ CH₂ H Cl SCF₃ H H CH₃ C₃H₇ — 1038 CH₃ CH₂ H Cl SCF₃ H H CH₃ C₄H₉ — 1039 CH₃ CH₂ H Cl SCF₃ H H CH₃ C₅H₁₁ — 1040 CH₃ CH₂ H Cl SCF₃ H H C₂H₅ C₄H₉ — 1041 CH₃ CH₂ H Cl SCF₃ H H C₃H₇ C₃H₅ — 1042 CH₃ CH₂ H Cl SCF₃ H H C₂H₅ C₂H₅ — 1044 CH₃ CH₂ H Cl CF₃ H H H 4-CH₃O—C₄H₄ 105-107 1045 CH₃ CH₂ H CF₃ Q3 H H c-C₃H₅ c-C₃H₅ 168-169 1046 CH₃ CH₂ H Cl Q3 H H c-C₃H₅ c-C₃H₅ 130-132 1047 CH₃ CH₂ H CF₃ SCH₃ H H c-C₃H₅ c-C₃H₅ — 1048 CH₃ CH₂ H Cl SCH₂ H H c-C₃H₅ c-C₃H₅ — 1049 CH₃ CH₂ H CF₃ COCH₃ H H c-C₃H₅ c-C₃H₅ — 1050 CH₃ CH₂ H Cl COCH₃ H H c-C₃H₅ c-C₃H₅ — 1051 CH₃ CH₂ H CF₃ CHCH₂ H H c-C₃H₅ c-C₃H₅ — — 1052 CH₃ CH₂ H Cl CHCH₂ H H c-C₃H₅ c-C₃H₅ — 1053 CH₃ CH₂ H Cl CH₃ H H H 4-CH₃O—C₆H₄ 113-115 1054 CH₃ CH₂ H OCH₃ OCH₃ H H H 4-CH₃O—C₆H₄ — 1055 CH₃ CH₂ H OCH₃ OCH₃ H H c-C₃H₅ c-C₃H₅ 128-130 1056 CH₃ CH₂ H OCH₃ OCH₃ H H C₂H₅ c-C₃H₅ — 1057 CH₃ CH₂ H OCH₃ OCH₃ H H CH₃ c-C₃H₅ — 1058 CH₃ CH₂ H OCH₃ OCH₃ H H CH₃ C₃H₇ — 1059 CH₃ CH₂ H OCH₃ OCH₃ H H CH₃ C₄H₉ — 1060 CH₃ CH₂ H OCH₃ OCH₃ H H CH₃ C₅H₁₁ — 1061 CH₃ CH₂ H OCH₃ OCH₃ H H C₂H₅ C₄H₉ — 1062 CH₃ CH₂ H OCH₃ OCH₃ H H C₃H₇ C₃H₇ — 1063 CH₃ CH₂ H OCH₃ OCH₃ H H C₂H₅ C₂H₅ — 1064 CH₃ CH₂ H OCH₃ CF₃ H H H 4-CH₃O—C₆H₄ — 1065 CH₃ CH₂ H OCH₃ CF₃ H H c-C₃H₅ c-C₃H₅ 158-159 1066 CH₃ CH₂ H OCH₃ CF₃ H H C₂H₅ c-C₃H₅ — 1067 CH₃ CH₂ H OCH₃ CF₃ H H CH₃ c-C₃H₅ — 1068 CH₃ CH₂ H OCH₃ CF₃ H H CH₃ C₃H₇ — 1069 CH₃ CH₂ H OCH₃ CF₃ H H CH₃ C₄H₉ — 1070 CH₃ CH₂ H OCH₃ CF₃ H H CH₃ C₅H₁₁ — 1071 CH₃ CH₂ H OCH₃ CF₃ H H C₂H₅ C₄H₉ — 1072 CH₃ CH₂ H OCH₃ CF₃ H H C₃H₇ C₃H₇ — 1073 CH₃ CH₂ H OCH₃ CF₃ H H C₂H₅ C₂H₅ — 1074 CH₃ CH₂ H CF₃ OCH₃ H H H 4-CH₃O—C₆H₄ oil 1075 CH₃ CH₂ H CF₃ OCH₃ H H c-C₃H₅ c-C₃H₅ 129-130 1076 CH₃ CH₂ H CF₃ OCH₃ H H C₂H₅ c-C₃H₅ 119-122 1077 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ c-C₃H₅ — 1078 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ C₃H₇ oil 1079 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ C₄H₉ oil 1080 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ C₅H₁₁ — 1081 CH₃ CH₂ H CF₃ OCH₃ H H C₂H₅ C₄H₉ — 1082 CH₃ CH₂ H CF₃ OCH₃ H H C₃H₇ C₃H₇ oil 1083 CH₃ CH₂ H CF₃ OCH₃ H H C₂H₅ C₂H₅ 77-78 1084 CH₃ CH₂ H OCH₃ Cl OCH₃ H H 4-CH₃O—C6H₉ — 1085 CH₃ CH₂ H OCH₃ Cl OCH₃ H c-C₃H₅ c-C₃H₅ — 1086 CH₃ CH₂ H OCH₃ Cl OCH₃ H C₂H₅ c-C₃H₅ — 1087 CH₃ CH₂ H OCH₃ Cl OCH₃ H CH₃ c-C₃H₅ — 1088 CH₃ CH₂ H OCH₃ Cl OCH₃ H CH₃ C₃H₇ — 1089 CH₃ CH₂ H OCH₃ Cl OCH₃ H CH₃ C₄H₉ — 1090 CH₃ CH₂ H OCH₃ Cl OCH₃ H CH₃ C₅H₁₁ — 1091 CH₃ CH₂ H OCH₃ Cl OCH₃ H C₂H₅ C₄H₉ — 1092 CH₃ CH₂ H OCH₃ Cl OCH₃ H C₃H₇ C₃H₇ — 1093 CH₃ CH₂ H OCH₃ Cl OCH₃ H C₂H₅ C₂H₅ — 1094 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H H 4-CH₃O—C₆H₄ — 1095 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 1096 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H C₂H₅ c-C₃H₅ — 1097 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H CH₃ c-C₃H₅ — 1098 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H CH₃ C₃H₇ — 1099 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H CH₃ C₄H₉ — 1100 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H CH₃ C₅H₁₁ — 1101 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H C₂H₅ C₄H₉ — 1102 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H C₃H₇ C₃H₇ — 1103 CH₃ CH₂ H OCH₃ CH₃ OCH₃ H C₂H₅ C₂H₅ — 1104 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H H 4-CH₃O—C₆H₄ — 1105 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 1106 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H C₂H₅ c-C₃H₅ — 1107 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H CH₃ c-C₃H₅ — 1108 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H CH₃ C₃H₇ — 1109 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H CH₃ C₄H₉ — 1110 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H CH₃ C₅H₁₁ — 1111 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H C₂H₅ C₄H₉ — 1112 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H C₃H₇ C₃H₅ — 1113 CH₃ CH₂ H OCH₃ CF₃ OCH₃ H C₂H₅ C₂H₅ — 1114 CH₃ CH₂ H OCH₃ CN OCH₃ H H 4-CH₃O—C₆H₄ — 1115 CH₃ CH₂ H OCH₃ CN OCH₃ H c-C₃H₅ c-C₃H₅ — 1116 CH₃ CH₂ H OCH₃ CN OCH₃ H C₂H₅ c-C₃H₅ — 1117 CH₃ CH₂ H OCH₃ CN OCH₃ H CH₃ c-C₃H₅ — 1118 CH₃ CH₂ H OCH₃ CN OCH₃ H CH₃ C₃H₇ — 1119 CH₃ CH₂ H OCH₃ CN OCH₃ H CH₃ C₄H₅ — 1120 CH₃ CH₂ H OCH₃ CN OCH₃ H CH₃ C₅H₁₁ — 1121 CH₃ CH₂ H OCH₃ CN OCH₃ H C₂H₅ C₄H₉ — 1122 CH₃ CH₂ H OCH₃ CN OCH₃ H C₃H₅ C₃H₇ — 1123 CH₃ CH₂ H OCH₃ CN OCH₃ H C₂H₅ C₂H₅ — 1124 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H H 4-CH₃O—C₆H₄ — 1125 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H c-C₃H₅ c-C₃H₅ — 1126 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H C₂H₅ c-C₃H₅ — 1127 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H CH₃ c-C₃H₅ — 1128 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H CH₃ C₃H₅ — 1129 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H CH₃ C₄H₉ — 1130 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H CH₃ C₅H₁₁ — 1131 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H C₂H₅ C₄H₉ — 1132 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H C₃H₇ C₃H₇ — 1133 CH₃ CH₂ H OCH₃ OCH₃ OCH₃ H C₂H₅ C₂H₅ — 1134 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂OSO₂CH₃ 110-111 1135 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂SCH₃ 134-135 1136 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂Cl 140-141 1137 CH₃ CH₂ H CH₃ CH₃ H CH₃ C₂H₅ CH₂CN 142-147 1138 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂OSO₂CH₃ — 1139 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂SCH₃ — 1140 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂Cl — 1141 CH₃ CH₂ H Cl Cl H H C₂H₅ CH₂CN — 1142 CH₃ CH₂ H Cl CF₃ H H C₂H₅ CH₂OSO₂CH₃ — 1143 CH₃ CH₂ H Cl CF₃ H H C₂H₅ CH₂SCH₃ — 1144 CH₃ CH₂ H Cl CF₃ H H C₂H₅ CH₂Cl — 1145 CH₃ CH₂ H Cl CF₃ H H C₂H₅ CH2CN — 1146 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ CH₂OSC2CH₃ — 1147 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ CHSSCH₃ — 1148 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ CH₂Cl — 1149 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ CH₂CN — 1150 CH₃ CH₂ H CF₃ OCH₃ H H C₃H₇ c-C₃H₅ oil 1151 CH₃ CH₂ H Cl CF₃ H H CH₃ C₃H7 97-98 1152 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₆H₅ c-C₃H₅ — 1153 CH₃ CH₂ H Cl CF₃ H H C₆H₅ c-C₃H₅ oil 1154 CH₃ CH₂ H Cl OCH₃ H H C₆H₅ c-C₃H₅ — 1155 CH₃ CH₂ H Cl OCF₃ H H C₆H₅ c-C₃H₅ oil 1156 CH₃ CH₂ H Cl CH₃ H H C₆H₅ c-C₃H₅ 119-120 1157 CH₃ CH₂ H CF₃ OCH₃ H H C₆H₅ c-C₃H₅ oil 1158 CH₃ CH₂ H Cl Cl H CH₃ C₆H₅ c-C₃H₅ oil 1159 CH₃ CH₂ H CH₃ OCH₃ Cl H C₆H₅ c-C₃H₅ — 1160 CH₃ CH₂ H CH₃ OCH₃ F H C₆H₅ c-C₃H₅ — 1161 CH₃ CH₂ H Cl Cl H H 4-F—C₆H₄ c-C₃H₅ oil 1162 CH₃ CH₂ H CH₃ OCH₃ CH₃ H 4-F—C₆H₄ c-C₃H₅ — 1163 CH₃ CH₂ H Cl CF₃ H H 4-F—C₆H₄ c-C₃H₅ oil 1164 CH₃ CH₂ H Cl OCH₃ H H 4-F—C₆H₄ c-C₃H₅ — 1165 CH₃ CH₂ H Cl OCF₃ H H 4-F—C₆H₄ c-C₃H₅ — 1166 CH₃ CH₂ H Cl CH₃ H H 4-F—C₆H₄ c-C₃H₅ — 1167 CH₃ CH₂ H CF₃ OCH₃ H H 4-F—C₆H₄ c-C₃H₅ — 1168 CH₃ CH₂ H Cl Cl H CH₃ 4-F—C₆H₄ c-C₃H₅ — 1169 CH₃ CH₂ H CH₃ OCH₃ Cl H 4-F—C₆H₄ C-C₃H₅ — 1170 CH₃ CH₂ H CH₃ OCH₃ F H 4-F—C₆H₄ c-C₃H₅ — 1171 CH₃ CH₂ H Cl Cl H H CH₃ c-C₄H₇ 109-110 1172 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ c-C₄H₇ — 1173 CH₃ CH₂ H Cl CF₃ H H CH₃ c-C₄H₇ 136-137 1174 CH₃ CH₂ H Cl OCH₃ H H CH₃ c-C₄H₇ — 1175 CH₃ CH₂ H Cl OCF₃ H H CH₃ c-C₄H₇ — 1176 CH₃ CH₂ H Cl CH₃ H H CH₃ c-C₄H₇ — 1177 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ c-C₄H₇ — 1178 CH₃ CH₂ H Cl Cl H CH₃ CH₃ c-C₄H₇ — 1179 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ c-C₄H₇ — 1180 CH₃ CH₂ H CH₃ OCH₃ F H CH₃ c-C₄H₇ — 1181 CH₃ CH₂ H Cl Cl H H C₂H₅ c-C₄H₇ — 1182 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₂H₅ c-C₄H₇ — 1183 CH₃ CH₂ H Cl CF₃ H H C₂H₅ c-C₄H₇ — 1184 CH₃ CH₂ H Cl OCH₃ H H C₂H₅ c-C₄H₇ — 1185 CH₃ CH₂ H Cl OCF₃ H H C₂H₅ c-C₄H₇ — 1186 CH₃ CH₂ H Cl CH₃ H H C₂H₅ c-C₄H₇ — 1187 CH₃ CH₂ H CF₃ OCH₃ H H C₂H₅ c-C₄H₇ — 1188 CH₃ CH₂ H Cl Cl H CH₃ C₂H₅ c-C₄H₇ — 1189 CH₃ CH₂ H CH₃ OCH₃ Cl H C₂H₅ c-C₄H₇ — 1190 CH₃ CH₂ H CH₃ OCH₃ F H C₂H₅ c-C₄H₇ — 1191 CH₃ CH₂ H Cl Cl H H C₃H₇ c-C₄H₇ — 1192 CH₃ CH₂ H CH₃ OCH₃ CH₃ H C₃H₇ c-C₄H₇ — 1193 CH₃ CH₂ H Cl CF₃ H H C₃H₇ c-C₄H₇ — 1194 CH₃ CH₂ H Cl OCH₃ H H C₃H₇ c-C₄H₇ — 1195 CH₃ CH₂ H Cl OCF₃ H H C₃H₇ c-C₄H₇ — 1196 CH₃ CH₂ H Cl CH₃ H H C₃H₇ c-C₄H₇ — 1197 CH₃ CH₃ H CF₃ OC₃ H H C₃H₇ c-C₄H₇ — 1198 CH₃ CH₂ H Cl Cl H CH₃ C₃H₇ c-C₄H₇ — 1199 CH₃ CH₂ H CH₃ OCH₃ Cl H C₃H₇ c-C₄H₇ — 1200 CH₃ CH₂ H CH₃ OCH₃ F H C₃H₇ c-C₄H₇ — 1201 CH₃ CH₂ H Cl Cl H H c-C₄H₇ c-C₄H₇ — 1202 CH₃ CH₂ H CH₃ OCH₂ CH₃ H c-C₄H₇ c-C₄H₇ — 1203 CH₃ CH₂ H Cl CF₃ H H c-C₄H₇ c-C₄H₇ — 1204 CH₃ CH₂ H Cl OCH₃ H H c-C₄H₇ c-C₄H₇ — 1205 CH₃ CH₂ H Cl OCF₃ H H c-C₄H₇ c-C₄H₇ — 1206 CH₃ CH₂ H Cl CH₃ H H c-C₄H₇ c-C₄H₇ — 1207 CH₃ CH₂ H CF₃ OCH₃ H H c-C₄H₇ c-C₄H₇ — 1208 CH₃ CH₂ H Cl Cl H CH₃ c-C₄H₇ c-C₄H₇ — 1209 CH₃ CH₂ H CH₃ OCH₃ Cl H c-C₄H₇ c-C₄H₇ — 1210 CH₃ CH₂ H CH₃ OCH₃ F H c-C₄H₅ c-C₄H₇ — 1211 CH₃ S H SCH₃ Cl H Cl C₂H₅ C₃H₇ 63-65 1212 CH₃ CH₂ H OCH₃ Cl H H c-C₃H₅ c-C₃H₅ 152-154 1213 CH₃ CH₂ H OCH₃ Cl H H C₂H₅ c-C₃H₅ — 1214 CH₃ CH₂ H OCH₃ Cl H H C₃H₇ c-C₃H₅ — 1215 CH₃ CH₂ H OCH₃ Cl H H CH₃ c-C₄H₇ — 1216 CH₃ CH₂ H OCH₃ Cl H H CH₃ C₃H₇ — 1217 CH₃ CH₂ H OCH₃ Cl H H C₂H₅ C₃H₇ — 1218 CH₃ CH₂ H OCH₃ Cl H H C₂H₅ C₂H₅ — 1219 CH₃ CH₂ H OCH₃ Cl H H C₃H₇ C₃H₇ — 1220 CH₃ CH₂ H OCH₃ Cl H H CH₃ C₄H₉ — 1221 CH₃ CH₂ H OCH₃ Cl H H H 4-CH₃O—C₆H₄ — 1222 CH₃ CH₂ H OCH₃ CH₃ H H c-C₃H₅ c-C₃H₅ oil 1223 CH₃ CH₂ H OCH₃ CH₃ H H C₂H₅ c-C₃H₅ — 1224 CH₃ CH₂ H OCH₃ CH₃ H H C₃H₇ c-C₃H₅ — 1225 CH₃ CH₂ H OCH₃ CH₃ H H CH₃ c-C₄H₇ — 1226 CH₃ CH₂ H OCH₃ CH₃ H H CH₃ C₃H₇ — 1227 CH₃ CH₂ H OCH₃ CH₃ H H C₂H₅ C₃H₇ — 1228 CH₃ CH₂ H OCH₃ CH₃ H H C₂H₅ C₂H₅ — 1229 CH₃ CH₂ H OCH₃ CH₃ H H C₃H₇ C₃H₇ — 1230 CH₃ CH₂ H OCH₃ CH₃ H H CH₃ C₄H₉ — 1231 CH₃ CH₂ H OCH₃ CH₃ H H H 4-CH₃O—C₆H₄ — 1232 CH₃ CH₂ H OCH₃ OCH₃ H F c-C₃H₅ c-C₃H₅ 176-178 1233 CH₃ CH₂ H OCH₃ OCH₃ H F C₂H₅ c-C₃H₅ — 1234 CH₃ CH₂ H OCH₃ OCH₃ H F C₃H₇ c-C₃H₅ — 1235 CH₃ CH₂ H OCH₃ OCH₃ H F CH₃ c-C₄H₇ — 1236 CH₃ CH₂ H OCH₃ OCH₃ H F CH₃ C₃H₇ — 1237 CH₃ CH₂ H OCH₃ OCH₃ H F C₂H₅ C₃H₇ — 1238 CH₃ CH₂ H OCH₃ OCH₃ H F C₂H₅ C₂H₅ — 1239 CH₃ CH₂ H OCH₃ OCH₃ H F C₃H₇ C₃H₇ — 1240 CH₃ CH₂ H OCH₃ OCH₃ H F CH₃ C₄H₉ — 1241 CH₃ CH₂ H OCH₃ OCH₃ H F H 4-CH₃O—C₆H₄ — 1242 CH₃ CH₂ H CF₃ F H H c-C₃H₅ c-C₃H₅ — 1243 CH₃ CH₂ H CF₃ F H H C₂H₅ c-C₃H₅ — 1244 CH₃ CH₂ H CF₃ F H H C₃H₇ c-C₃H₅ 115-118 1245 CH₃ CH₂ H CF₃ F H H CH₃ c-C₄H₇ — 1246 CH₃ CH₂ H CF₃ F H H CH₃ C₃H₇ — 1247 CH₃ CH₂ H CF₃ F H H C₂H₅ C₃H₇ — 1248 CH₃ CH₂ H CF₃ F H H C₂H₅ C₂H₅ — 1249 CH₃ CH₂ H CF₃ F H H C₃H₇ C₃H₇ — 1250 CH₃ CH₂ H CF₃ F H H CH₃ C₄H₉ — 1251 CH₃ CH₂ H CF₃ F H H H 4-CH₃O—C₆H₄ 57-70 1252 CH₃ CH₂ H CF₃ F H H BnOCH₂ BnOCH₂ oil 1253 CH₃ CH₂ H CF₃ F H H CH₃ C₆H₅ 119-120 1254 CH₃ CH₂ H CF₃ F H H C₆H₅ C₆H₅ 135-139 1255 CH₃ CH₂ H Cl OCF₃ H H C₃H₇ c-C₃H₅ oil 1256 CH₃ CH₂ H Cl OCF₃ H H C₂H₅ C₃H₇ oil 1257 CH₃ CH₂ H Cl CF₃ H H H CH₂═CH—CH═CH 83-85 1258 CH₃ CH₂ H CF₃ CF₃ H H c-C₃H₅ c-C₃H₅ 163-165 1259 CH₃ CH₂ H CF₃ OH H H c-C₃H₅ c-C₃H₅ 245-246 1260 CH₃ CH₂ H CF₃ OC₃H₇ H H c-C₃H₅ c-C₃H₅ 127-128 1261 CH₃ CH₂ H CF₃ OC₃H₇ H H C₂H₅ c-C₃H₅ — 1262 CH₃ CH₂ H CF₃ OC₃H₇ H H C₃H₇ c-C₃H₅ — 1263 CH₃ CH₂ H CF₃ OC₃H₇ H H CH₃ c-C₄H₇ — 1264 CH₃ CH₂ H CF₃ OC₃H₇ H H CH₃ C₃H₇ — 1265 CH₃ CH₂ H CF₃ OC₃H₇ H H C₂H₅ C₃H₇ — 1266 CH₃ CH₂ H CF₃ OC₃H₇ H H C₂H₅ C₂H₅ — 1267 CH₃ CH₂ H CF₃ OC₃H₇ H H C₃H₇ C₃H₇ — 1268 CH₃ CH₂ H CF₃ OC₃H₇ H H CH₃ C₄H₅ — 1269 CH₃ CH₂ H CF₃ OC₃H₇ H H H 4-CH₂O—C₄H₄ — 1284 CH₃ CH₂ H CH₃ OH F H c-C₃H₅ c-C₃H₅ — 1285 CH₃ CH₂ H CH₃ OH F H C₂H₅ c-C₃H₅ — 1286 CH₃ CH₂ H CH₃ OH F H C₃H₇ c-C₃H₅ — 1287 CH₃ CH₂ H CH₃ OH F H CH₃ c-C₄H₇ — 1288 CH₃ CH₂ H CH₃ OH F H CH₃ C₃H₇ — 1289 CH₃ CH₂ H CH₃ OH F H C₂H₅ C₃H₇ — 1290 CH₃ CH₂ H CH₃ OH F H C₂H₅ C₂H₅ — 1291 CH₃ CH₂ H CH₃ OH F H C₃H₇ C₃H₇ — 1292 CH₃ CH₂ H CH₃ OH F H CH₃ C₄H₉ — 1293 CH₃ CH₂ H CH₃ OH F H H 4-CH₂O—C₆H₄ — 1294 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H CH₃ CH₃ 101-102 1295 CH₃ CH₂ H CH₃ OCH₃ OCH₃ H CH₃ C₂H₅ oil 1296 CH₃ CH₂ H Cl Cl H H C₂H₅ 4-CH₃O—C₆H₄ oil 1297 CH₃ CH₂ H Cl Cl H CH₃ C₂H₅ C₂H₅ 133-135 1298 CH₃ CH₂ H Cl Cl H CH₃ C₂H₅ C₃H₇ 123-125 1299 CH₃ CH₂ H Cl Cl H CH₃ C₃H₇ C₃H₇ 125-127 1300 CH₃ CH₂ H Cl Cl H CH₃ C₂H₅ c-C₃H₅ 157-159 1301 CH₃ O H CH₃ OCH₃ CH₃ H c-C₃H₅ c-C₃H₅ — 1302 CH₃ O H Cl CF₃ H H c-C₃H₅ c-C₃H₅ 149-150 1303 CH₃ O H Cl OCH₃ H H c-C₃H₅ c-C₃H₅ 124-125 1304 CH₃ O H Cl OCF₃ H H c-C₃H₅ c-C₃H₅ — 1305 CH₃ O H Cl CH₃ H H c-C₃H₅ c-C₃H₅ — 1306 CH₃ O H CF₃ OCH₃ H H c-C₃H₅ c-C₃H₅ — 1307 CH₃ O H Cl Cl H CH₃ c-C₃H₅ c-C₃H₅ — 1308 CH₃ O H CH₃ OCH₃ Cl H c-C₃H₅ c-C₃H₅ — 1309 CH₃ O H CH₃ OCH₃ F H c-C₃H₅ c-C₃H₅ — 131 CH₃ O H CH₃ OCH₃ CH₃ H CH₃ C₃H₇ — 1311 CH₃ O H Cl CF₃ H H CH₃ C₃H₇ — 1312 CH₃ O H Cl OCH₃ H H CH₃ C₃H₇ — 1313 CH₃ O H Cl OCF₃ H H CH₃ C₃H₇ — 1314 CH₃ O H Cl CH₃ H H CH₃ C₃H₇ — 1315 CH₃ O H CF₃ OCH₃ H H CH₃ C₃H₇ — 1316 CH₃ O H Cl Cl H CH₃ CH₃ C₃H₇ — 1317 CH₃ O H CH₃ OCH₃ Cl H CH₃ C₃H₇ — 1318 CH₃ O H CH₃ OCH₃ F H CH₃ C₃H₇ — 1319 CH₃ CH₂ H Cl Cl H H C₆H₅ C₃H₇ oil 1320 CH₃ CH₂ H Cl Cl H H C₆H₅ CH₃ oil 1321 CH₃ CH₂ H Cl Cl H H c-C₃H₅ 2-CH₂—C₆H₄ oil 1322 CH₃ CH₂ H Cl Cl H H C₄H₉ CH(CH₂OH)₂ oil 1323 CH₃ CH₂ H Cl Cl H H C₆H₅ CO₂C₂H₅ oil 1324 CH₃ CH₂ H Cl Cl H H C₆H₅ CO₂H oil 1325 CH₃ CH₂ H Cl Cl H H C₆H₅ CH₂CH oil 1326 CH₃ CH₂ H CH₃ OCH₃ Cl H H 2-Cl—C₆H₄ oil 1327 CH₃ CH₂ H CH₃ OCH₃ Cl H H 3-Cl—C₆H₄ oil 1328 CH₃ CH₂ H CH₃ OCH₃ Cl H H 4-Cl—C₆H₄ oil 1329 CH₃ CH₂ H CH₃ OCH₃ Cl H H 3-CH₃O—C₆H₄ oil 1330 CH₃ CH₂ H CH₃ OCH₃ Cl H H 3-CN—C₆H₄ oil 1331 CH₃ CH₂ H CH₃ OCH₃ Cl H H 4-CN—C₆H₄ oil 1332 CH₃ CH₂ H CH₃ OCH₃ Cl H H 4-BnO—C₆H₉ oil 1333 CH₃ CH₂ H CH₃ OCH₃ Cl H H 2,5-(CH₃O)— oil C₆H₃ 1334 CH₃ CH₂ H CH₃ OCH₃ Cl H H 2-CH₃O—C₆H₄ oil 1335 CH₃ CH₂ H Cl Cl H H CN c-C₃H₅ oil 1336 CH₃ CH₂ H Cl Cl H H CH₃ CH₂OC₂H₅ 96-97 1337 CH₃ CH₂ H Cl Cl H H H CH(OH)CH₂OC₆H₅ oil 1338 CH₃ CH₂ H Cl Cl H H H CH(OH)CH₂C₆H₅ oil 1339 CH₃ CH₂ H Cl Cl H H H CH(OH)C₃H₇ oil 1340 CH₃ CH₂ H Cl Cl H H CH(CH₃)₂ C(O)-1- 154-155 morpholinyl 1341 CH₃ CH₂ H Cl Cl H H C₂H₅ CO₂CH₃ oil 1342 CH₃ CH₂ H Cl Cl H H CH₃ CO₂CH₃ oil 1343 CH₃ CH₂ H Cl Cl H H CH₃ CN oil 1344 CH₃ CH₂ H Cl Cl H H CH₃ COCH₃ oil 1345 CH₃ CH₂ H Cl Cl H H H 2-Cl—C₆H₄ 149-152 1346 CH₃ CH₂ H Cl Cl H H H 3-Cl—C₆H₄ oil 1347 CH₃ CH₂ H Cl Cl H H H 4-F—C₆H₄ 148-149 1348 CH₃ CH₂ H Cl Cl H H H 4-CN—C₆H₄ 199-200 1349 CH₃ CH₂ H Cl Cl H H H 4-Cl—C₆H₄ 183-184 1350 CH₃ CH₂ H Cl Cl H H c-C₃H₅ c-C₄H₇ — 1351 CH₃ CH₂ H CH₃ OCH₃ CH₃ H c-C₃H₅ c-C₄H₇ — 1352 CH₃ CH₂ H Cl CF₃ H H c-C₃H₅ c-C₄H₇ — 1353 CH₃ CH₂ H Cl OCH₃ H H c-C₃H₅ c-C₄H₇ — 1354 CH₃ CH₂ H Cl OCF₃ H H c-C₃H₅ c-C₄H₇ — 1355 CH₃ CH₂ H Cl CH₃ H H c-C₃H₅ c-C₄H₇ — 1356 CH₃ CH₂ H CF₃ OCH₃ H H c-C₃H₅ c-C₄H₇ — 1357 CH₃ CH₂ H Cl Cl H CH₃ c-C₃H₅ c-C₄H₇ — 1358 CH₃ CH₂ H CH₃ OCH₃ Cl H c-C₃H₅ c-C₄H₇ — 1359 CH₃ CH₂ H CH₃ OCH₃ F H c-C₃H₅ c-C₄H₇ — 1360 CH₃ CH₂ H Cl OCH₃ F H c-C₃H₅ c-C₃H₅ — 1361 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ c-C₃H₅ — 1362 CH₃ CH₂ H Cl OCH₃ F H C₃H₇ c-C₃H₅ — 1363 CH₃ CH₂ H Cl OCH₃ F H CH₃ c-C₄H₇ — 1364 CH₃ CH₂ H Cl OCH₃ F H CH₃ C₃H₇ — 1365 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ C₃H₇ — 1366 CH₃ CH₂ H Cl OCH₃ F H C₂H₅ C₂H₅ — 1367 CH₃ CH₂ H Cl OCH₃ F H C₃H₇ C₃H₅ — 1368 CH₃ CH₂ H Cl OCH₃ F H CH₃ C₄H₉ — 1369 CH₃ CH₂ H Cl OCH₃ F H H 4-CH₃O—C₆H₄ — 1370 CH₃ CH₂ H CF₃ OCH₃ H H C₂H₅ C₃H₇ oil 1371 CH₃ CH₂ H Cl Cl H H CH₃ 2-CH₃c-C₃H₄ oil 1372 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ 2-CH₃c-C₃H₄ — 1373 CH₃ CH₂ H Cl CF₃ H H CH₃ 2-CH₃c-C₃H₄ — 1374 CH₃ CH₂ H Cl OCH₂ H H CH₃ 2-CH₃c-C₃H₄ — 1375 CH₃ CH₂ H Cl OCF H H CH₃ 2-CH₃c-C₃H₄ — 1376 CH₃ CH₂ H Cl CH₃ H H CH₃ 2-CH₃c-C₃H₄ — 1377 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ 2-CH₃c-C₃H₄ — 1378 CH₃ CH₂ H Cl Cl H CH₃ CH₃ 2-CH₃c-C₃H₄ — 1379 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ 2-CH₃c-C₃H₄ — 1380 CH₃ CH₂ H Cl Cl H H CH₃ 2-CH₃c-C₃H₄ — 1381 CH₃ CH₂ H Cl Cl H H CH₃ 2-C₆H₅-c-C₃H₄ — 1382 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ 2-C₆H₅-c-C₃H₄ — 1383 CH₃ CH₂ H Cl CF₃ H H CH₃ 2-C₆H₅-c-C₃H₄ — 1384 CH₃ CH₂ H Cl OCH₃ H H CH₃ 2-C₆H₅-c-C₃H₄ — 1385 CH₃ CH₂ H Cl OCF₃ H H CH₃ 2-C₆H₅-c-C₃H₄ — 1386 CH₃ CH₂ H Cl CH₃ H H CH₃ 2-C₆H₅-c-C₃H₄ — 1387 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ 2-C₆H₅-c-C₃H₄ — 1388 CH₃ CH₂ H Cl Cl H CH₃ CH₃ 2-C₆H₅-c-C₃H₄ — 1389 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ 2-C₆H₅-c-C₃H₄ — 1390 CH₃ CH₂ H Cl Cl H H CH₃ 2-C₆H₅-c-C₃H₄ — 1391 CH₃ CH₂ H Cl Cl H H CH₃ 2-(2- — pyridyl)- c-C₃H₄ 1392 CH₃ CH₂ H CH₃ OCH₃ CH₃ H CH₃ 2-(2- — pyridyl)- c-C₃H₄ 1393 CH₃ CH₂ H Cl CF₃ H H CH₃ 2-(2- — pyridyl)- c-C₃H₄ 1394 CH₃ CH₂ H Cl OCH₃ H H CH₃ 2-(2- — pyridyl)- c-C₃H₄ 1395 CH₃ CH₂ H Cl OCF₃ H H CH₃ 2-(2- — pyridyl)- c-C₃H₄ 1396 CH₃ CH₂ H Cl CH₃ H H CH₃ 2-(2- — pyridyl)- c-C₃H₄ 1397 CH₃ CH₂ H CF₃ OCH₃ H H CH₃ 2-(2- — pyridyl)- c-C₃H₄ 1398 CH₃ CH₂ H Cl Cl H CH₃ CH₃ 2-(2- — pyridyl)- c-C₃H₄ 1399 CH₃ CH₂ H CH₃ OCH₃ Cl H CH₃ 2-(2- — pyridyl)- c-C₃H₄ 1400 CH₂ O H Cl Cl H H CH₃ 2-(2- — pyridyl)- c-C₃H₄

Key:

(a) Where the compound is indicated as an “oil”, data is provided below: Example 3 spectral data: TLC R_(F) 0.27 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.90 (1H, s), 6.95 (2H, s), 4.45 (1H, br), 4.27-4.17 (2H, m), 3.85 (1H, dd, J=9.5, 4.8 Hz), 3.27 (3H, s), 2.94 (2H, q, J=7.5 Hz), 2.56-2.46 (1H, m), 2.32 (3H, s), 2.06 (3H, s), 2.03 (3H, s), 1.37 (3H, t, J=7.5 Hz), 0.85 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 355 (3), 354 (25), 353 (100). Analysis calc'd for C₂₁H₂₈N₄O.1.5H₂O: C, 66.46; H, 8.23; N, 14.76; found: C, 67.00; H, 8.10; N, 14.38.

Example 8 spectral data: TLC R_(F) 0.34 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 6.95 (2H, s), 4.46 (1H, br), 3.41-3.33 (1H, m), 3.22 (3H, s), 2.94 (2H, q, J=7.3 Hz), 2.93-2.85 (1H, m), 2.84-2.69 (2H, m), 2.51 (1H, br), 2.32 (3H, s), 2.30-2.20 (1H, m), 2.04 (6H, s), 1.37 (3H, t, J=7.7 Hz), 0.84 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₂H₃₀N₄O: 366.2420, found 366.2400; 369 (3), 368 (27), 367 (100).

Example 10 spectral data: TLC R_(F) 0.13 (ethyl acetate). ¹H NMR (300 MHz, CDCl₃): δ8.93 (1H, s), 8.10 (1H, s), 7.96 (1H, s), 6.96 (2H, s), 4.39 (1H, br), 4.24-4.14 (1H, m), 4.12-4.00 (1H, m), 3.20 (1H, br), 2.80 (2H, q, J=7.0 Hz), 2.78-2.68 (1H, m), 2.42 (1H, br), 2.33 (3H, s), 2.13-2.04 (1H, m), 2.06 (3H, s), 2.03 (3H, s), 1.33 (3H, t, J=7.5 Hz), 0.80 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₃H₃₀N₇: 404.2563, found 404.2556; 406 (4), 405 (28), 404 (100).

Example 11 spectral data: TLC R_(F) 0.60 (ethyl acetate). ¹H NMR (300 MHz, CDCl₃): δ8.92 (1H, s), 8.51 (1H, s), 6.96 (2H, s), 4.78-4.68 (1H, m), 4.57-4.47 (1H, m), 4.32-4.22 (1H, m), 3.43 (1H, br), 2.81 (2H, q, J=6.9 Hz), 2.78 (1H, br), 2.43 (1H, br), 2.33 (3H, s), 2.10-2.00 (1H, m), 2.07 (3H, s), 2.03 (3H, s), 1.32 (3H, t, J=7.0 Hz), 0.78 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₂₂H₂₉N₈: 405.2515, found 405.2509; 407 (4), 406 (27), 405 (100).

Example 18 spectral data: TLC R_(F) 0.20 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.00 (1H, s), 7.26 (1H, obscurred), 6.96 (2H, s), 6.86-6.76 (3H, m), 5.46 (2H, s), 3.76 (3H, s), 2.85 (2H, q, J=7.7 Hz), 2.33 (3H, s), 2.06 (6H, s), 1.28 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e 389 (4), 388 (28), 387 (100). Analysis calc'd for C₂₄H₂₆N₄O: C, 74.58; H, 6.78; N, 14.50; found: C, 74.36; H, 6.73; N, 13.83.

Example 27 spectral data: TLC R_(F) 0.20 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 6.95 (2H, s), 4.25 (2H, t, J=7.5 Hz), 2.93 (2H, q, J=7.7 Hz), 2.32 (3H, s), 2.04 (6H, s), 1.91-1.86 (2H, m), 1.50-1.38 (2H, m), 1.39 (3H, t, J=7.7 Hz), 1.01 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 325 (3), 324 (23), 323 (100).

Example 28 spectral data: TLC R_(F) 0.28 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 6.95 (2H, s), 4.24 (2H, t, J=7.9 Hz), 2.93 (2H, q, J=7.6 Hz), 2.32 (3H, s), 2.04 (6H, s), 1.90 (2H, m), 1.44-1.36 (7H, m), 0.93 (3H, t, J=7.1 Hz). MS (NH₃-CI): m/e 339 (3), 338 (25), 337 (100). Analysis calc'd for C₂₁H₂₈N₄: C, 74.96; H, 8.40; N, 16.65; found: C, 74.24; H, 8.22; N, 16.25.

Example 34 spectral data: MS (ESI): m/e 365 (M+2), 363 (M+H⁺, 100%).

Example 35 spectral data: TLC R_(F) 0.31 (20:80 ethyl acetate-hexane). ¹H,NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.71 (1H, d, J=8.4 Hz), 7.58 (1H, d, J=1.8 Hz), 7.41 (1H, dd, J=8.4, 1.8 Hz), 4.27 (1H, br), 2.95 (2H, q, J=7.3 Hz), 2.41 (2H, br), 2.11-1.98 (2H, br), 1.42 (3H, t, J=7.3 Hz), 1.37-1.20 (3H, m), 1.09-0.99 (1H, m), 0.84 (3H, t, J=7.7 Hz), 0.82 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e calc'd for C₂₀H₂₅N₄Cl₂: 391.1456, found 391.1458; 395 (11), 394 (14), 393 (71), 392 (29), 391 (100)

Example 38 spectral data: MS (NH₃-CI): m/e 375 (M+H⁺, 100%).

Example 40 spectral data: MS (NH₃-CI): m/e 377 (M+H⁺, 100%).

Example 48 spectral data: MS (NH₃-CI): m/e 423 (M+H⁺, 100%).

Example 50 spectral data: TLC R_(F) 0.27 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.03 (1H, s), 7.70 (1H, d, J=8.0 Hz), 7.59 (1H, d, J=1.8 Hz), 7.41 (1H, dd, J=8.0, 1.8 Hz), 7.36-7.30 (2H, m), 7.24-7.19 (3H, m), 5.50 (2H, s), 2.87 (2H, q, J=7.5 Hz), 1.31 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₂₀H₁₆N₄Cl₂: 382.0752, found 382.0746; 388 (3), 387 (12), 386 (16), 385 (66), 384 (26), 383 (100).

Example 51 spectral data: MS (NH₃-CI): m/e 413 (M+H⁺, 100%).

Example 54 spectral data: MS (NH₃-CI): m/e 459 (M+H⁺, 100%).

Example 68 spectral data: TLC R_(F) 0.28 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 6.69 (2H, s), 4.30-4.19 (1H, m), 3.82 (3H, s), 2.92 (2H, q, J=7.6 Hz), 2.41 (1H, br), 2.08 (3H, s), 2.07 (3H, s), 2.06 (1H, br), 1.38 (3H, t, J=7.6 Hz), 1.36-1.22 (4H, m), 1.10-0.98 (1H, m), 0.96-0.87 (1H, m), 0.84 (3H, t, J=7.0 Hz), 0.81 (3H, t, J=6.7 Hz). MS (NH₃-CI): m/e 383 (4), 382 (27), 381 (100).

Example 122 spectral data: TLC R_(F) 0.10 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.97 (1H, s), 6.94 (2H, s), 4.14 (2H, d, J=7.7 Hz), 3.48 (1H, q, J=7.0 Hz), 2.63 (3H, s), 2.31 (3H, s), 2.01 (6H, s), 1.43-1.19 (8H, m), 0.94 (3H, t, J=7.3 Hz), 0.84 (3H, t, J=7.0 Hz). MS (NH₃-CI): m/e 367 (3), 366 (25), 365(100).

Example 123 spectral data: TLC R_(F) 0.24 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.97 (1H, s), 6.94 (2H, s), 4.25 (2H, t, J=8.1 Hz), 3.48 (1H, q, J=7.1 Hz), 2.63 (3H, s), 2.31 (3H, s), 2.01 (6H, s), 1.81 (2H, m), 1.47-1.19 (8H, m), 0.91 (6H, m). MS (NH₃-CI): m/e 381 (4), 380 (27), 379 (100). Analysis calc'd for C₂₄H₃₄N₄: C, 76.15; H, 9.05; N, 14.80; found: C, 76.29; H, 9.09; N, 14.75.

Example 202 spectral data: TLC R_(F) 0.20 (10:90 ethyl acetate-hexane). 1H NMR (300 MHZ, CDCl₃): d 8.82 (1H, s), 6.96 (2H, s), 4.46-4.38 (1H, m), 4.13 (3H, s), 2.34 (3H, s), 2.28-2.11 (2H, m), 2.07 (6H, s), 1.95-1.81 (2H, m), 1.38-1.17 (3H, m), 1.14-0.99 (1H, m), 0.83 (3H, t, J=7.7 Hz), 0.80 (3H, t, J=7.7 Hz). MS (NH3-CI): m/e calc'd for C₂₂H₃₀N₄O: 366.2420, found 366.2408; 369 (4), 368 (26), 367 (100).

Example 404 spectral data: TLC R_(F) 0.20 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃) δ6.93 (2H, s), 4.20 (2H, t, J=7.7 Hz), 2.90 (2H, q, J=7.6 Hz), 2.83 (3H, s), 2.30 (6H, s), 1.88 (2H, m), 1.42-1.34 (7H, m), 0.93 (3H, t, J=6 Hz). MS (NH₃-CI): m/e 353 (3), 352 (27), 351 (100).

Example 414 spectral data: TLC R_(F) 0.36 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.92 (1H, s), 7.66 (1H, d, J=8.1 Hz), 7.32-7.26 (2H, m), 4.54 (1H, m), 2.95 (2H, q, J=7.4 Hz), 2.43 (3H, s), 2.39 (1H, m), 2.03 (1H, m), 1.74 (3H, d, J=7.0 Hz), 1.41 (3H, t, J=7.5 Hz), 1.31 (1H, m), 1.16 (1H, m), 0.92 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₁₉H₂₄N₄Cl: 343.1690, found 343.1704; 346 (7), 345 (34), 344, (23), 343 (100).

Example 415 spectral data: TLC R_(F) 0.25 (10:90 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.71 (1H, d, J=8.1 Hz), 7.34-7.30 (2H, m), 4.30-4.20 (1H, m), 2.94 (2H, q, J=7.5 Hz), 2.50-2.35 (2H, m), 2.44 (3H, s), 2.08-1.95 (2H, m), 1.43 (3H, t, J=7.5 Hz), 1.29 (3H, m), 1.08-0.98 (1H, m), 0.84 (3H, t, J=7.0 Hz), 0.81 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e 374 (7), 373 (33), 372 (25), 371 (100). Analysis calc'd for C₂₁H₂₇ClN₄: C, 68.00; H, 7.35; N, 15.10; found: C, 68.25; H, 7.30; N, 14.85.

Example 424 spectral data: TLC R_(F) 0.28 (5:95 ethyl acetate-dichloromethane). ¹H NMR (300 MHz, CDCl₃): δ8.95 (1H, s), 7.60 (1H, d, J=7.7 Hz), 7.37 (1H, d, J=0.8 Hz), 7.21 (1H, dd, J=7.7, 0.8 Hz), 4.58-4.50 (1H, m), 2.96 (2H, dq, J=7.5, 2.0 Hz), 2.46-2.33 (1H, m), 2.40 (3H, s), 2.08-1.96 (1H, m), 1.74 (3H, d, J=6.6 Hz), 1.40 (3H, t, J=7.5 Hz), 1.39-1.22 (1H, m), 1.20-1.08 (1H, m), 0.92 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₁₉H₂₄ClN₄: 343.1690, found 343.1697; 346 (8), 345 (38), 344 (25), 343 (100).

Example 434 spectral data: TLC R_(F) 0.78 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.90 (1H, s), 6.95 (2H, s), 2.97 (2H, J=7.3 Hz), 2.60-2.50 (1H, m), 2.41-2.33 (1H, m), 2.32 (3H, s), 2.20-2.10 (1H, m), 2.05 (3H, s), 2.02 (3H, s), 1.85-1.80 (1H, m), 1.39 (3H, t, J=7.5 Hz), 0.85 (3H, t, J=7.5 Hz), 0.50-0.35 (2H, m), 0.25-0.15 (1H, m), 0.10-0.00 (1H, m). MS (NH₃-CI): m/e calc'd for C₂₃H₃₀N₄: 362.2470, found 362.2458; 365 (4), 364 (27), 363 (100).

Example 436 spectral data: TLC R_(F) 0.31 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.88 (1H, s), 7.77 (1H, d, J=9.2 Hz), 6.87 (2H, m), 4.40-4.25 (1H, m), 3.86 (3H, s), 2.99 (2H, q, J=7.5 Hz), 2.60-2.35 (2H, m), 2.47 (3H, s), 2.15-2.00 (1H, m), 1.80-1.70 (1H, m), 1.45 (3H, t, J=7.5 Hz), 0.84 (3H, t, J=7.5 Hz), 0.50-0.35 (2H, m), 0.30-0.20 (1H, m), 0.10-0.00 (1H, m), −0.85-−0.95 (1H, m).

Example 437 spectral data: TLC R_(F) 0.25 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.90 (1H, s), 7.73 (1H, d, J=9.2 Hz), 6.89-6.86 (2H, m), 4.58-4.51 (1H, m), 3.86 (3H, s), 2.95 (2H, dq, J=7.6, 1.8 Hz), 2.47 (3H, s), 2.45-2.34 (1H, m), 2.07-1.97 (1H, m), 1.73 (3H, d, J=7.0 Hz), 1.42 (3H, t, J=7.6 Hz), 1.40-1.27 (1H, m), 1.20-1.07 (1H, m), 0.92 (3H, t, J=7.4 Hz). MS (NH₃-CI): m/e calc'd for C₂₀H₂₇N₄O: 339.2185, found 339.2187; 341 (3), 340 (22), 339 (100). Analysis calc'd for C₂₀H₂₆N₄O: C, 70.98; H, 7.74; N, 16.55; found: C, 69.97; H, 7.48; N, 15.84.

Example 438 spectral data: TLC R_(F) 0.42 (40:60 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.98 (1H, s), 7.77 (1H, d, J=9.1 Hz), 7.17 (2H, d, J=8.8 Hz), 6.90-6.83 (4H, m), 5.42 (2H, s), 3.86 (3H, s), 3.78 (3H, s), 2.86 (2H, q, J=7.5 Hz), 2.49 (3H, s), 1.33 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 391 (4), 390 (26), 389 (100). Analysis calc'd for C₂₃H₂₄N₄O₂: C, 71.11; H, 6.24; N, 14.42; found: C, 71.14; H, 5.97; N, 14.03.

Example 439 spectral data: TLC R_(F) 0.41 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 7.77 (1H, d, J=3.1 Hz), 6.89 (2H, m), 3.86 (3H, s), 3.53 (1H, m), 2.91 (2H, q, J=7.5 Hz), 2.49 (3H, s), 2.28 (1H, m), 2.21 (1H, m), 1.43 (3H, t, J=7.3 Hz), 0.86 (3H, t, J=7.3 Hz), 0.78 (2H, m), 0.46 (2H, m), 0.20 (1H, m).

Example 440 spectral data: TLC R_(F) 0.28 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 7.73 (1H, d, J=9.1 Hz), 6.90-6.86 (2H, m), 4.60-4.40 (1H, m), 3.86 (3H, s), 2.95 (2H, dq, J=7.7, 2.2 Hz), 2.47 (3H, s), 2.44-2.36 (1H, m), 2.05-1.98 (1H, m), 1.74 (3H, d, J=7.0 Hz), 1.42 (3H, t, J=7.5 Hz), 1.40-1.20 (5H, m), 1.13-1.05 (1H, m), 0.830 (3H, t, J=6.6 Hz).

Example 502 spectral data: TLC R_(F) 0.63 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.92 (1H, s), 6.95 (2H, s), 4.60-4.47 (1H, m), 2.93 (2H, q, J=7.7 Hz), 2.43-2.33 (1H, m), 2.32 (3H, s), 2.16-2.06 (1H, m), 2.05 (3H, s), 2.03 (3H, s), 1.76 (3H, d, J=7.0 Hz), 1.36 (3H, t, J=7.7 Hz), 1.36-1.20 (4H, m), 0.86 (3H, t, J=7.2 Hz). MS (NH₃-CI): m/e calc'd for C₂₂H₃₀N₄: 350.2470, found 350.2480; 353 (3), 352 (28), 351 (100).

Example 503 spectral data: ¹H NMR (300 MHz, CDCl₃): δ8.92 (1H, s), 6.94 (2H, s), 4.58-4.48 (1H, m), 2.93 (2H, q, J=7.3 Hz), 2.32 (3H, s), 2.05 (3H, s), 2.02 (3H, s), 1.76 (3H, d, J=6.6 Hz), 1.36 (3H, t, J=7.3 Hz), 1.34-1.05 (8H, m), 0.88 (3H, t, J=7 Hz). MS (NH₃-CI): m/e calc'd for C₂₃H₃₂N₄: 365.2705, found 365.2685; 367 (3), 366 (27), 365 (100).

Example 506 spectral data: TLC R_(F) 0.28 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.95 (1H, s), 7.67 (1H, d, J=8.4 Hz), 7.57 (1H, d, J=1.8 Hz), 7.42-7.37 (1H, m), 4.56 (1H, hextet, J=7.1 Hz), 2.99 (2H, q, J=7.5 Hz), 2.43-2.33 (1H, m), 2.09-1.97 (1H, m), 1.74 (3H, d, J=7.0 Hz), 1.41 (3H, t, J=7.5 Hz), 1.35-1.07 (2H, m), 0.92 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e 367 (12), 366 (14), 365 (67), 3.64 (24), 363 (100).

Example 507 spectral data: MS (NH₃-CI): m/e 377 (M+H⁺, 100%).

Example 511 spectral data: TLC R_(F) 0.51 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.97 (1H, s), 7.87 (1H, d, J=8.1 Hz), 7.83 (1H, d, J=1.1 Hz), 7.68 (1H, dd, J=8.1, 1.1 Hz), 3.60-3.51 (1H, m), 2.94 (2H, q, J=7.5 Hz), 2.53-2.39 (1H, m), 2.36-2.20 (1H, m), 1.96 (1H, br), 1.42 (3H, t, J=7.5 Hz), 0.88 (3H, t, J=7.3 Hz), 0.88-0.78 (1H, m), 0.52-0.44 (2H, m), 0.24-0.16 (1H, m). MS (NH₃-CI): m/e 412 (7), 411 (33), 410 (23), 409 (100).

Example 513 spectral data: TLC R_(F) 0.62 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.97 (1H, s), 7.87 (1H, d, J=8.0 Hz), 7.83 (1H, d, J=0.7 Hz), 7.68 (1H, dd, J=8.0, 0.7 Hz), 4.21 (1H, br), 2.96 (2H, q, J=7.5 Hz), 2.42 (2H, br), 2.12-1.97 (2H, m), 1.43 (3H, t, J=7.5 Hz), 1.40-1.20 (4H, m), 0.85 (3H, t, J=7.3 Hz), 0.83 (3H, t, J=7.6 Hz). MS (NH₃-CI): m/e 428 (8), 427 (38), 426 (29), 425 (100).

Example 514 spectral data: TLC R_(F) 0.51 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.86 (1H, d, J=8.1 Hz), 7.83 (1H, d, J=0.8 Hz), 7.68 (1H, dd, J=8.1, 0.8 Hz), 4.20 (1H, br), 2.97 (2H, q, J=7.7 Hz), 2.54-2.39 (2H, m), 2.15-2.01 (2H, m), 1.43 (3H, t, J=7.7 Hz), 0.84 (6H, t, J=7.5 Hz). MS (NH₃-CI): m/e 400 (7), 399 (37), 398 (26), 397 (100).

Example 524 spectral data: TLC R_(F) 0.50 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 7.76 (1H, d, J=9.1 Hz), 6.90-6.87 (2H, m), 4.35 (1H, v br), 3.86 (3H, s), 2.93 (2H, q, J=7.6 Hz), 2.48 (3H, s), 2.39 (2H, br), 2.00-1.90 (2H, m), 1.43 (3H, t, J=7.6 Hz), 1.38-1.22 (2H, m), 1.18-1.02 (2H, m), 0.90 (6H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₂H₃₁N₄O: 367.2498, found 367.2506; 369 (3), 368 (25), 367 (100).

Example 526 spectral data: TLC R_(F) 0.28 (10:90 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.69 (1H, d, J=8.1 Hz), 7.34-7.30 (2H, m), 4.40-4.35 (1H, m), 2.93 (2H, q, J=7.4 Hz), 2.44 (3H, s), 2.38 (2H, m), 1.96 (2H, m), 1.43 (3H, t, J=7.5 Hz), 1.35-1.22 (2H, m), 1.15-1.05 (2H, m), 0.90 (6H, t, J=7.1 Hz). MS (NH₃-CI): m/e 374 (8), 373 (35), 372 (25), 371 (100). Analysis calc'd for C₂₁H₂₇N₄Cl: C, 68.00; H, 7.35; N, 15.10; found: C, 67.89; H, 7.38; N, 14.94.

Example 528 spectral data: TLC R_(F) 0.65 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.97 (1H, s), 7.86 (1H, d, J=8.0 Hz), 7.82 (1H, d, J=1.1 Hz), 7.67 (1H, dd, J=8.0, 1.1 Hz), 4.38 (1H, br), 2.95 (2H, q, J=7.5 Hz), 2.39 (2H, br), 2.04-1.92 (2H, br), 1.42 (3H, t, J=7.5 Hz), 1.40-1.21 (3H, m), 1.19-1.03 (1H, m), 0.91 (6H, t, J=7.3 Hz). MS (NH₃-CI): m/e 428 (8), 427 (37), 426 (27), 425 (100).

Example 538 spectral data: TLC R_(F) 0.56 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.88 (1H, d, J=8.0 Hz), 7.83 (1H, d, J=0.8 Hz), 7.68 (1H, dd, J=8.0, 0.8 Hz), 3.77 (1H, br), 2.95 (2H, q, J=7.5 Hz), 2.61 (1H, br), 2.08 (1H, br), 1.45 (3H, t, J=7.5 Hz), 1.36-1.25 (1H, m), 1.17 (3H, d, J=6.6 Hz), 0.71 (3H, t, J=7.3 Hz), 0.69 (3H, d, J=7.0 Hz). MS (NH₃-CI): m/e 414 (7), 413 (33), 412 (24), 411 (100).

Example 534 spectral data: MS (ESI): m/e 363 (M+2), 361 (M⁺, 100 %).

Example 544 spectral data: TLC R_(F) 0.63 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.90 (1H, s), 7.74 (1H, d, J=9.1 Hz), 6.89-6.86 (2H, m), 3.86 (3H, s), 3.79-3.73 (1H, m), 2.93 (3H, dq, J=7.7, 2.6 Hz), 2.49 (3H, s), 2.03-1.99 (1H, m), 1.81 (3H, d, J=6.9 Hz), 1.41 (3H, t, J=7.3 Hz), 0.84-0.74 (2H, m), 0.53-0.41 (2H, m), 0.28-0.21 (1H, m).

Example 548 spectral data: TLC R_(F) 0.42 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.99 (1H, s), 7.84 (1H, d, J=7.7 Hz), 7.82 (1H, d, J=0.9 Hz), 7.68 (1H, dd, J=7.7, 0.9 Hz), 3.83-3.70 (1H, m), 3.00-2.90 (2H, m), 2.09-1.98 (1H, m), 1.83 (3H, d, J=7.0 Hz), 1.40 (3H, t, J=7.3 Hz), 0.88-0.78 (1H, m), 0.57-0.41 (2H, m), 0.30-0.20 (1H, m). MS (NH₃-CI): m/e 398 (6), 397 (31), 396 (22), 395 (100).

Example 551 spectral data: TLC R_(F) 0.56 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.93 (1H, s), 6.94 (2H, s), 4.75 (1H, heptet, J=7.0 Hz), 2.95 (2H, q, J=7.7 Hz), 2.32 (3H, s), 2.04 (6H, s), 1.80 (6H, d, J=7.0 Hz), 1.36 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e 311 (4), 310 (34), 309 (100); Analysis calc'd for C₁₉H₂₄N₄.0.5H₂O: C, 71.89; H, 7.94; N, 17.65; found: C, 71.59; H, 7.83; N, 17.41.

Example 558 spectral data: TLC R_(F) 0.53 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.98 (1H, s), 7.86-7.81 (2H, m), 7.67 (1H, dd, J=8.4, 1.1 Hz), 4.60-4.48 (1H, m), 3.01-2.93 (2H, m), 2.49-2.35 (1H, m), 2.13-2.00 (1H, m), 1.76 (3H, d, J=7.0 Hz), 1.41 (3H, t, J=7.5 Hz), 1.40-1.20 (4H, m), 0.87 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e 414 (8), 413 (38), 412 (27), 411 (100).

Example 564 spectral data: TLC R_(F) 0.34 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 7.77 (1H, d, J=9.2 Hz), 6.89 (2H, m), 4.30-4.20 (1H, m), 3.86 (3H, s), 2.93 (2H, q, J=7.5 Hz), 2.48 (3H, s), 2.45-2.35 (2H, m), 2.10-1.95 (2H, m), 1.44 (3H, t, J=7.5 Hz), 1.40-1.20 (3H, m), 1.10-0.95 (1H, m), 0.84 (3H, t, J=7.3 Hz), 0.81 (3H, t, J=7.3 Hz).

Example 571 spectral data: TLC R_(F) 0.40 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 6.95 (2H, s), 4.51 (1H, br), 3.44-3.24 (4H, m), 2.96 (2H, q, J=7.3 Hz), 2.95-2.87 (1H, m), 2.85-2.75 (1H, m), 2.59-2.49 (1H, m), 2.32 (3H, s), 2.27-2.18 (1H, m), 2.04 (3H, s), 2.04 (3H, s), 1.38 (3H, t, J=7.7 Hz), 1.12 (3H, t, J=7.0 Hz), 0.84 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₃H₃₂N₄O: 380.2576, found 380.2554; 383 (4), 382 (28), 381 (100).

Example 581 spectral data: TLC R_(F) 0.33 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 6.95 (2H, s), 4.49-4.39 (1H, m), 4.23-4.13 (1H, m), 3.91 (1H, dd, J=9.9, 4.8 Hz), 3.48 (1H, dq, J=9.1, 7.0 Hz), 3.30 (1H, dq, J=9.1, 7.0 Hz), 2.95 (2H, q, J=7.7 Hz), 2.60-2.47 (1H, m), 2.32 (3H, s), 2.15-2.01 (1H, m), 2.04 (3H, s), 2.03 (3H, s), 1.37 (3H, t, J=7.5 Hz), 1.00 (3H, t, J=7.0 Hz), 0.86 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₂H₃₁N₄O: 367.2498, found 367.2497; 369 (4), 368 (27), 367 (100).

Example 591 spectral data: TLC R_(F) 0.42 (50:50 ethyl acetate-hexane). 1H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 6.95 (2H, s), 3.76 (1H, br), 3.47-3.40 (1H, m), 3.21 (3H, s), 2.99-2.90 (1H, m), 2.88 (2H, q, J=7.3 Hz), 2.76 (1H, br), 2.51-2.41 (1H, m), 2.32 (3H, s), 2.09 (1H, br), 2.08 (3H, s), 2.04 (3H, s), 1.35 (3H, t, J=7.3 Hz), 0.84-0.76 (1H, m), 0.56-0.44 (2H, m), 0.30-0.21 (1H, m). MS (NH₃-CI): m/e calc'd for C₂₃H₃₁N₄O: 379.2498, found 379.2514; 381 (4), 380 (27), 379 (100).

Example 690 spectral data: TLC R_(F) 0.12 (30:70 ethyl acetate-hexane). 1H NMR (300 MHz, CDCl₃): d 9.01 (1H, s), 7.38-7.22 (5H, m), 6.75 (1H, s), 6.69 (1H, s), 5.48 (2H, s), 3.70 (3H, s), 2.84 (2H, q, J=7.7 Hz), 2.37 (3H, s), 2.05 (3H, s), 1.26 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e 375 (4), 374 (28), 373 (100).

Example 692 spectral data: TLC R_(F) 0.32 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.98 (1H, s), 7.48 (1H, s), 7.37-7.18 (5H, m), 7.11 (1H, s), 5.49 (2H, s), 2.84 (2H, q, J=7.3 Hz), 2.38 (3H, s), 2.29 (6H, s), 1.31 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₃H₂₄N₄: 356.2001, found 356.1978; 359 (4), 358 (28), 357 (100).

Example 693 spectral data: TLC R_(F) 0.22 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.90 (1H, s), 7.78 (1H, d, J=9.5 Hz), 6.90-6.87 (2H, m), 3.86 (3H, s), 3.62 (1H, br), 2.91 (2H, q, J=7.5 Hz), 2.50 (3H, s), 2.40 (1H, br), 2.26-2.13 (1H, m), 1.92 (1H, br), 1.58 (1H, br), 1.43 (3H, t, J=7.5 Hz), 1.35-1.25 (1H, m), 1.13-1.03 (1H, m), 0.95-0.75 (2H, m), 0.85 (3H, t, J=7.1 Hz), 0.54-0.42 (2H, m), 0.22-0.17 (1H, m). MS (NH₃-CI): m/e 381 (4), 380 (25), 379 (100).

Example 697 spectral data: TLC R_(F) 0.28 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 7.74 (1H, d, J=9.5 Hz), 6.90-6.86 (2H, m), 4.58-4.45 (1H, m), 2.95 (2H, dq, J=7.7, 2.2 Hz), 2.48 (3H, s), 2.45-2.35 (1H, m), 2.09-1.99 (1H, m), 1.74 (3H, d, J=7.0 Hz), 1.42 (3H, t, J=7.5 Hz), 1.37-1.23 (3H, m), 1.11-1.03 (1H, m), 0.86 (3H, t, J=7.0 Hz).

Example 724 spectral data: TLC R_(F) 0.45 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.92 (1H, s), 7.75 (1H, d, J=8.4 Hz), 7.09 (1H, d, J=2.6 Hz), 6.96 (1H, dd, J=8.4, 2.6 Hz), 3.87 (3H, s), 3.76 (1H, br), 2.94 (2H, q, J=7.3 Hz), 2.61 (1H, br), 2.09 (1H, br), 1.45 (3H, t, J=7.3 Hz), 1.36-1.26 (1H, m), 1.15 (3H, d, J=6.6 Hz), 0.71 (3H, t, J=7.3 Hz), 0.68 (3H, d, J=6.6 Hz). MS (NH₃-CI): m/e 377 (1), 376 (8), 375 (38), 374 (25), 373 (100).

Example 725 spectral data: TLC R_(F) 0.31 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.88 (1H, s), 7.80 (1H, d, J=9.2 Hz), 6.89 (2H, m), 3.86 (3H, s), 3.75 (1H, m), 2.92 (2H, q, J=7.4 Hz), 2.60 (1H, m), 2.48 (3H, s), 2.05 (1H, m), 1.46 (3H, t, J=7.4 Hz), 1.16 (3H, d, J=7.0 Hz), 0.70 (3H, t, J=7.3 Hz), 0.67 (3H, d, J=6.6 Hz).

Example 727 spectral data: TLC R_(F) 0.44 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.90 (1H, s), 7.84 (1H, d, J=2.2 Hz), 7.74 (1H, d, J=8.4 Hz), 7.65 (1H, dd, J=8.4, 2.2 Hz), 3.76 (1H, br), 2.93 (1H, q, J=7.3 Hz), 2.60 (1H, br), 2.08 (1H, br), 1.42 (3H, t, J=7.3 Hz), 1.37-1.27 (1H, m), 1.16 (3H, d, J=7.0 Hz), 0.69 (3H, t, J=7.3 Hz), 0.67 (3H, d, J=7.0 Hz). MS (NH₃-CI): m/e 414 (7), 413 (33), 412(27), 411 (100).

Example 750 spectral data: TLC R_(F) 0.42 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.73 (1H, d, J=8.4 Hz), 7.10 (1H, d, J=2.6 Hz), 6.96 (1H, dd, J=8.4, 2.6 Hz), 3.87 (3H, s), 3.63 (1H, v br), 2.92 (2H, q, J=7.3 Hz), 2.38 (1H, br), 2.22-2.10 (1H, m), 1.94 (1H, br), 1.42 (3H, t, J=7.3 Hz), 1.41-1.29 (1H, m), 1.23-1.08 (1H, m), 0.91 (3H, t, J=7.3 Hz), 0.89-0.79 (1H, m), 0.51-0.41 (2H, m), 0.25-0.15 (1H, m). MS (NH₃-CI): m/e 388 (8), 387 (34), 386 (25), 385 (100).

Example 751 spectral data: TLC R_(F) 0.36 (40:60 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 7.77 (1H, d, J=9.1 Hz), 6.90 (2H, m), 3.86 (3H, s), 3.62 (1H, m), 2.84 (2H, q, J=7.5 Hz), 2.49 (3H, s), 2.40 (1H, m), 2.19 (1H, m), 1.90 (1H, m), 1.43 (3H, t, J=7.5 Hz), 1.38 (1H, m), 1.19 (1H, m), 0.91 (3H, t, J=7.3 Hz), 0.80 (1H, m), 0.49 (2H, m), 0.21 (1H, m).

Example 753 spectral data: TLC R_(F) 0.44 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.92 (1H, s), 7.84 (1H, d, J=1.8 Hz), 7.73 (1H, d, J=8.5 Hz), 7.65 (1H, dd, J=8.5, 1.8 Hz), 3.65 (1H, br), 2.92 (1H, q, J=7.5 Hz), 2.38 (1H, br), 2.25-2.14 (1H, m), 1.94 (1H, br), 1.43-1.26 (1H, m), 1.40 (3H, t, J=7.5 Hz), 1.21-1.06 (1H, m), 0.92 (3H, t, J=7.3 Hz), 0.91-0.79 (1H, m), 0.52-0.44 (2H, m), 0.22-0.16 (1H, m). MS (NH₃-CI): m/e 426 (9), 425 (42), 424 (31), 423 (100).

Example 767 spectral data: MS (NH₃-CI): m/e 379 (M+H⁺, 100%).

Example 776 spectral data: TLC R_(F) 0.41 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.93 (1H, s), 7.73 (1H, d, J=8.4 Hz), 7.09 (1H, d, J=2.6 Hz), 6.96 (1H, dd, J=8.4, 2.6 Hz), 4.28 (1H, br), 3.87 (3H, s), 2.95 (2H, q, J=7.3 Hz), 2.41 (2H, br), 2.10-1.93 (2H, m), 1.43 (3H, t, J=7.3 Hz), 1.40-1.23 (1H, m), 1.18-1.03 (1H, m), 0.91 (3H, t, J=7.3 Hz), 0.82 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₂₀H₂₆ClN₄O: 373.1795, found 373.1815; 376 (8), 375 (35), 374 (24), 373 (100).

Example 777 spectral data: TLC R_(F) 0.46 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 7.76 (1H, d, J=9.0 Hz), 6.90-6.87 (2H, m), 4.29 (1H, br), 3.86 (3H, s), 2.94 (2H, q, J=7.4 Hz), 2.48 (3H, s), 2.40 (2H, br), 2.10-1.92 (2H, m), 1.44 (3H, t, J=7.4 Hz), 1.37-1.22 (1H, m), 1.18-1.02 (1H, m), 0.90 (3H, t, J=7.3 Hz), 0.81 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₁H₂₉N₄O: 353.2341, found 353.2328; 355 (3), 354 (23), 353 (100).

Example 778 spectral data: TLC R_(F) 0.58 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.97 (1H, s), 7.86 (1H, d, J=8.0 Hz), 7.83 (1H, d, J=0.8 Hz), 7.68 (1H, dd, J=8.0, 0.8 Hz), 4.30 (1H, br), 2.96 (2H, q, J=7.5 Hz), 2.41 (2H, br), 2.11-1.95 (2H, m), 1.43 (3H, t, J=7.5 Hz), 1.42-1.22 (2H, m), 0.92 (3H, t, J=7.3 Hz), 0.83 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e 414 (8), 413 (39), 412 (28), 411 (100).

Example 779 spectral data: TLC R_(F) 0.44 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.84 (1H, d, J=1.8 Hz), 7.72 (1H, d, J=8.0 Hz), 7.65 (1H, dd, J=8.0, 1.8 Hz), 4.31 (1H, br), 2.94 (1H, q, J=7.5 Hz), 2.40 (2H, br), 2.10-1.93 (2H, m), 1.40 (3H, t, J=7.5 Hz), 1.37-1.21 (1H, m), 1.19-1.02 (1H, m), 0.91 (3H, t, J=7.3 Hz), 0.81 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e 414 (9), 413 (43), 412 (31), 411 (100).

Example 793 spectral data: MS (NH₃-CI): m/e 367 (M+H⁺, 100%).

Example 799 spectral data: TLC R_(F) 0.61 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.90 (1H, s), 7.47 (1H, s), 7.10 (1H, s), 4.28 (1H, br), 2.93 (2H, q, J=7.3 Hz), 2.41 (1H, br), 2.36 (3H, s), 2.28 (6H, s), 2.07-1.91 (3H, m), 1.42 (3H, t, J=7.3 Hz), 1.35-1.21 (1H, m), 1.19-1.03 (1H, m), 0.90 (3H, t, J=7.2 Hz), 0.81 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₂H₃₀N₄: 350.2470, found 350.2476; 353 (3), 352 (24), 351 (100).

Example 802 spectral data: TLC R_(F) 0.38 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.92 (1H, s), 7.84 (1H, d, J=1.8 Hz), 7.73 (1H, d, J=8.4 Hz), 7.65 (1H, dd, J=8.4, 1.8 Hz), 3.53 (1H, br), 2.91 (1H, q, J=7.4 Hz), 2.52-2.35 (1H, m), 2.34-2.20 (1H, m), 1.95 (1H, br), 1.40 (3H, t, J=7.4 Hz), 0.89-0.79 (1H, m), 0.87 (3H, t, J=7.3 Hz), 0.55-0.42 (2H, m), 0.25-0.15 (1H, m). MS (NH₃-CI): m/e 412 (8), 411 (41), 410 (29), 409 (100).

Example 803 spectral data: TLC R_(F) 0.33 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.93 (1H, s), 7.85 (1H, d, J=2.2 Hz), 7.71 (1H, d, J=8.4 Hz), 7.64 (1H, dd, J=8.4, 2.2 Hz), 3.77 (1H, dq, J=9.9, 7.0 Hz), 2.93 (1H, dq, J=7.5, 2.0 Hz), 2.09-1.98 (1H, m), 1.82 (3H, d, J=7.0 Hz), 1.39 (3H, t, J=7.5 Hz), 0.86-0.78 (1H, m), 0.59-0.50 (1H, m), 0.49-0.40 (1H, m), 0.29-0.20 (1H, m). MS (NH₃-CI): m/e 399 (2), 398 (8), 397 (39), 396 (24), 395 (100).

Example 804 spectral data: TLC R_(F) 0.31 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.92 (1H, s), 7.84 (1H, d, J=1.8 Hz), 7.71-7.62 (2H, m), 4.55 (1H, m), 2.95 (2H, q, J=7.5 Hz), 2.43-2.32 (1H, m), 2.10-1.98 (1H, m), 1.75 (3H, d, J=7.0 Hz), 1.39 (3H, t, J=7.5 Hz), 1.38-1.27 (1H, m), 1.19-1.09 (1H, m), 0.93 (3H, t, J=7.1 Hz). MS (NH₃-CI): m/e 400 (7), 399 (32), 398 (22), 397 (100). Analysis calc'd for C₁₉H₂₀ClF₃N₄: C, 57.51; H, 5.08; N, 14.12; found: C, 57.55; H, 5.06; N, 13.95.

Example 805 spectral data: TLC R_(F) 0.41 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.92 (1H, s), 7.84 (1H, d, J=1.8 Hz), 7.70 (1H, d, J=8.0 Hz), 7.64 (1H, dd, J=8.0, 1.8 Hz), 4.58-4.49 (1H, m), 2.95 (1H, q, J=7.5 Hz), 2.45-2.33 (1H, m), 2.11-2.00 (1H, m), 1.75 (3H, d, J=6.6 Hz), 1.39 (3H, t, J=7.5 Hz), 1.38-1.21 (4H, m), 0.86 (3H, t, J=7.0 Hz). MS (NH₃-CI): m/e 414 (8), 413 (40), 412 (29), 411 (100).

Example 807 spectral data: TLC R_(F) 0.49 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.84 (1H, d, J=1.8 Hz), 7.73 (1H, d, J=8.4 Hz), 7.65 (1H, dd, J=8.4, 1.8 Hz), 4.38-4.19 (1H, m), 2.94 (1H, q, J=7.5 Hz), 2.40 (2H, br), 2.10-1.98 (2H, m), 1.41 (3H, t, J=7.5 Hz), 1.38-1.20 (3H, m), 1.09-0.99 (1H, m), 0.84 (3H, t, J=7.0 Hz), 0.81 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 428 (7), 427 (32), 426 (25), 425 (100).

Example 808 spectral data: TLC R_(F) 0.51 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.84 (1H, d, J=1.8 Hz), 7.72 (1H, d, J=8.4 Hz), 7.64 (1H, dd, J=8.4, 1.8 Hz), 4.37 (1H, br), 2.93 (1H, q, J=7.5 Hz), 2.38 (2H, br), 2.02-1.90 (2H, m), 1.40 (3H, t, J=7.5 Hz), 1.38-1.20 (2H, m), 1.18-1.01 (2H, m), 0.90 (6H, t, J=7.3 Hz). MS (NH₃-CI): m/e 428 (8), 427 (39), 426 (30), 425 (100).

Example 809 spectral data: TLC R_(F) 0.40 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.90 (1H, s), 7.84 (1H, d, J=2.2 Hz), 7.72 (1H, d, J=8.1 Hz), 7.65 (1H, dd, J=8.1, 2.2 Hz), 4.20 (1H, br), 2.94 (1H, q, J=7.5 Hz), 2.51-2.38 (2H, m), 2.13-2.00 (2H, m), 1.41 (3H, t, J=7.5 Hz), 0.82 (6H, t, J=7.5 Hz). MS (NH₃-CI): m/e 400 (7), 399 (36), 398 (25), 397 (100).

Example 824 spectral data: TLC R_(F) 0.27 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 8.10 (1H, s), 7.94 (1H, d, J=8.8 Hz), 7.87 (1H, d, J=8.1 Hz), 4.56 (1H, m), 2.96 (2H, q, J=7.5 Hz), 2.40 (1H, m), 2.10-2.00 (1H, m), 1.76 (3H, d, J=7.0 Hz), 1.39 (3H, t, J=7.5 Hz), 1.33-1.10 (2H, m), 0.93 (3H, t, J=7.1 Hz). ¹⁹F NMR (300 MHz, CDCl₃): δ−58.2, −63.4. MS (NH₃-CI): m/e 433 (3), 432 (24), 431 (100).

Example 832 spectral data: TLC R_(F) 0.34 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.73 (1H, d, J=8.5 Hz), 7.10 (1H, d, J=2.6 Hz), 6.96 (1H, dd, J=8.5, 2.6 Hz), 3.87 (3H, s), 3.55 (1H, br), 2.92 (2H, q, J=7.3 Hz), 2.53-2.35 (1H, m), 2.31-2.18 (1H, m), 1.96 (1H, br), 1.42 (3H, t, J=7.3 Hz), 0.87 (3H, t, J=7.5 Hz), 0.87-0.79 (1H, m), 0.53-0.43 (2H, m), 0.25-0.15 (1H, m). MS (NH₃-CI): m/e 374 (8), 373 (34), 372 (24), 371 (100).

Example 833 spectral data: TLC R_(F) 0.20 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.70 (1H, d, J=8.4 Hz), 7.10 (1H, d, J=2.5 Hz), 6.96 (1H, dd, J=8.4, 2.5 Hz), 4.16 (2H, d, J=7.0 Hz), 3.87 (3H, s), 3.01 (2H, q, J=7.3 Hz), 1.46 (3H, t, J=7.3 Hz), 1.37-1.27 (1H, m), 0.66-0.52 (4H, m). MS (NH₃-CI): m/e 346 (6), 345 (32), 344 (23), 343 (100).

Example 834 spectral data: TLC R_(F) 0.18 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.69 (1H, d, J=8.4 Hz), 7.09 (1H, d, J=1 Hz), 6.96 (1H, dd, J=8.4, 1 Hz), 4.60-4.50 (1H, m), 3.87 (3H, s), 2.97 (2H, q, J=7.3 Hz), 2.49-2.33 (1H, m), 2.09-1.97 (1H, m), 1.74 (3H, d, J=7.0 Hz), 1.41 (3H, t, J=7.5 Hz), 1.40-1.22 (1H, m), 1.21-1.09 (1H, m), 0.92 (3H, t, J=7.1 Hz). MS (NH₃-CI): m/e calc'd for C₁₉H₂₄ClN₄O: 359.1639, found 359.1623; 362 (7), 361 (33), 360 (23), 359 (100). Analysis calc'd for C₁₉H₂₃ClN₄O.0.5 H₂O: C, 62.20; H, 6.32; N, 15.27; found: C, 62.33; H, 6.36; N, 14.86.

Example 835 spectral data: TLC R_(F) 0.39 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.69 (1H, d, J=8.4 Hz), 7.09 (1H, d, J=2.5 Hz), 6.95 (1H, dd, J=8.4, 2.5 Hz), 4.53-4.47 (1H, m), 3.87 (3H, s), 3.01-2.92 (2H, m), 2.48-2.35 (1H, m), 2.11-1.99 (1H, m), 1.74 (3H, d, J=6.9 Hz), 1.41 (3H, t, J=7.5 Hz), 1.38-1.22 (3H, m), 1.14-1.00 (1H, m), 0.86 (3H, t, J=7.1 Hz). MS (NH₃-CI): m/e 376 (7), 375 (33), 374 (23), 373 (100).

Example 836 spectral data: TLC R_(F) 0.42 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.79 (1H, d, J=8.8 Hz), 7.09 (1H, d, J=2.5 Hz), 6.95 (1H, dd, J=8.8, 2.5 Hz), 4.55-4.47 (1H, m), 3.87 (3H, s), 3.01-2.92 (2H, m), 2.48-2.35 (1H, m), 2.10-1.97 (1H, m), 1.74 (3H, d, J=7.0 Hz), 1.41 (3H, t, J=7.5 Hz), 1.35-1.20 (5H, m), 1.18-1.02 (1H, m), 0.84 (3H, t, J=7.0 Hz). MS (NH₃-CI): m/e calc'd for C₂₁H₂₈ClN₄O: 387.1952, found 387.1944; 391 (1), 390 (8), 389 (35), 388 (25), 387 (100).

Example 837 spectral data: TLC R_(F) 0.45 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.93 (1H, s), 7.73 (1H, d, J=8.8 Hz), 7.09 (1H, d, J=2.6 Hz), 6.96 (1H, dd, J=8.8, 2.6 Hz), 4.25 (1H, br), 3.87 (3H, s), 2.95 (2H, q, J=7.3 Hz), 2.41 (2H, br), 2.10-2.00 (2H, m), 1.43 (3H, t, J=7.3 Hz), 1.37-1.20 (3H, m), 1.12-0.98 (1H, m), 0.84 (3H, t, J=7.3 Hz), 0.82 (3H, t, J=7.4 Hz). MS (NH₃-CI): m/e 390 (8), 389 (34), 388 (25), 387 (100).

Example 838 spectral data: TLC R_(F) 0.48 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.72 (1H, d, J=8.5 Hz), 7.09 (1H, d, J=2.2 Hz), 6.96 (1H, dd, J=8.5, 2.2 Hz), 4.36 (1H, v br), 3.87 (3H, s), 2.94 (2H, q, J=7.3 Hz), 2.39 (2H, br), 2.02-1.90 (2H, m), 1.42 (3H, t, J=7.3 Hz), 1.39-1.21 (2H, m), 1.18-1.03 (2H, m), 0.90 (6H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₁H₂₈ClN₄O: 387.1952, found 387.1958; 391 (1), 390 (8), 389 (34), 388 (26), 387 (100).

Example 839 spectral data: TLC R_(F) 0.36 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.93 (1H, s), 7.73 (1H, d, J=8.5 Hz), 7.09 (1H, d, J=2.6 Hz), 6.96 (1H, dd, J=8.5, 2.6 Hz), 4.19 (1H, br s), 3.87 (3H, s), 2.96 (2H, q, J=7.5 Hz), 2.52-2.38 (2H, m), 2.13-1.99 (2H, m), 1.43 (3H, t, J=7.5 Hz), 0.83 (6H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₁₉H₂₄ClN₄O: 359.1639, found 359.1632; 362 (7), 361 (34), 360 (23), 359 (100).

Example 870 spectral data: MS (NH₃-CI): m/e 423 (M+H⁺, 100%).

Example 900 spectral data: TLC R_(F) 0.38 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.93 (1H, s), 7.75 (1H, d, J=9.2 Hz), 6.90-6.86 (2H, m), 4.23 (2H, t, J=7.7 Hz), 3.86 (3H, s), 2.95 (2H, q, J=7.7 Hz), 2.48 (3H, s), 1.93-1.83 (2H, m), 1.45 (3H, t, J=7.6 Hz), 1.43-1.36 (4H, m), 0.92 (3H, t, J=7.0 Hz).

Example 902 spectral data: TLC R_(F) 0.28 (5:95 ethyl acetate-dichloromethane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.63 (1H, d, J=8.1 Hz), 7.37 (1H, d, J=1.0 Hz), 7.21 (1H, dd, J=8.1, 1.0 Hz), 4.38 (1H, br), 2.94 (2H, q, J=7.5 Hz), 2.41 (3H, s), 2.40 (2H, br), 2.00-1.90 (2H, m), 1.42 (3H, t, J=7.5 Hz), 1.35-1.22 (2H, m), 1.17-1.03 (2H, m), 0.90 (6H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₁H₂₈ClN₄: 371.2002, found 371.1993; 374 (8), 373 (34), 372 (25), 371 (100).

Example 944 spectral data: MS (NH₃-CI): m/e 377 (M+H⁺, 100%).

Example 945 spectral data: MS (NH₃-CI): m/e 365 (M+H⁺, 100%).

Example 947 spectral data: MS (NH₃-CI): m/e 353 (M+H⁺, 100%).

Example 951 spectral data: MS (NH₃-CI): m/e 381 (M+H⁺, 100%).

Example 952 spectral data: MS (NH₃-CI): m/e 353 (M+H⁺, 100%).

Example 1003 spectral data: TLC R_(F) 0.10 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.99 (1H, s), 7.43 (1H, s), 7.19 (2H, d, J=8.8 Hz), 6.86 (2H, d, J=8.8 Hz), 6.84 (1H, s), 5.42 (2H, s), 3.94 (3H, s), 3.91 (3H, s), 3.78 (3H, s), 2.86 (2H, q, J=7.7 Hz), 2.45 (3H, s), 1.35 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e 421 (4), 420 (27), 419 (100). Analysis calculated for C₂₄H₃₆N₄O₃: C, 68.88; H, 6.26; N, 13.39; found: C, 68.53; H, 6.30; N, 12.96.

Example 1012 spectral data: m.p. 147-148° C. TLC R_(F) 0.18 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.88 (1H, s), 7.60 (1H, s), 6.77 (1H, s), 4.61 (2H, t, J=8.6 Hz), 3.44 (1H, v br), 3.24 (2H, t, J=8.6 Hz), 2.94 (2H, br), 2.44 (3H, s), 2.03 (2H, v br), 1.45 (3H, br t, J=6 Hz), 0.89-0.79 (2H, m), 0.58 (2H, br), 0.50-0.40 (2H, m), 0.27-0.17 (2H, m). MS (NH₃-CI): m/e 377 (4), 376 (27), 375 (100). Analysis calc'd for C₂₃H₂₆N₄O: C, 73.77; H, 7.01; N, 14.96; found: C, 73.69; H, 7.08; N, 14.40.

Example 1023 spectral data: TLC R_(F) 0.22 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.04 (1H, s), 7.78 (1H, d, J=8.4 Hz), 7.44 (1H, d, J=1.1 Hz), 7.30 (1H, dd, J=8.4, 1.1 Hz), 7.20 (2H, d, J=8.5 Hz), 6.87 (2H, d, J=8.5 Hz), 5.44 (2H, s), 3.79 (3H, s), 2.90 (2H, q, J=7.5 Hz), 1.32 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 467 (1), 466 (8), 465 (35), 464 (27), 463 (100).

Example 1027 spectral data: TLC R_(F) 0.41 (25:75 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.76 (1H, d, J=8.4 Hz), 7.45-7.44 (1H, m), 7.27 (1H, dm, J=8 Hz), 4.61-4.51 (1H, m), 2.98 (2H, dq, J=7.5, 1.6 Hz), 2.48-2.35 (1H, m), 2.10-1.98 (1H, m), 1.75 (3H, d, J=7.0 Hz), 1.41 (3H, t, J=7.5 Hz), 1.35-1.22 (2H, m), 0.93 (3H, t, J=7.2 Hz). MS (NH₃-CI): m/e calculated for C₁₉H₂₁ClF₃N₄O: 413.1349, found 413.1344; 416 (8), 415 (35), 414 (24), 413 (100).

Example 1028 spectral data: TLC R_(F) 0.45 (25:75 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.77 (1H, d, J=8.4 Hz), 7.44 (1H, m), 7.27 (1H, dm, J=8 Hz), 4.57-4.49 (1H, m), 2.97 (2H, dq, J=7.7, 1.7 Hz), 2.47-2.36 (1H, m), 2.12-2.02 (1H, m), 1.75 (3H, d, J=7.0 Hz), 1.41 (3H, t, J=7.7 Hz), 1.33-1.21 (4H, m), 0.86 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calculated for C₂₀H₂₃ClF₃N₄O: 427.1509, found 427.1507; 430 (8), 429 (35), 428 (25), 427 (100).

Example 1032 spectral data: TLC R_(F) 0.44 (25:75 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.95 (1H, s), 7.80 (1H, d, J=8.4 Hz), 7.45-7.44 (1H, m), 7.30 (1H, dm, J=8 Hz), 4.23-4.17 (1H, m), 2.97 (2H, q, J=7.6 Hz), 2.54-2.39 (2H, m), 2.14-2.00 (2H, m), 1.43 (3H, t, J=7.6 Hz), 0.84 (6H, t, J=7.3 Hz). MS (NH₃-CI): m/e calculated for C₁₉H₂₁ClF₃N₄O: 413.1368, found 413.1373; 416 (8), 415 (34), 414 (24), 413 (100).

Example 1150 spectral data: TLC R_(F) 0.23 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.90 (1H, s), 7.73 (1H, d, J=8.8 Hz), 7.36 (1H, d, J=2.6 Hz), 7.17 (1H, dd, J=8.8, 2.6 Hz), 3.92 (3H, s), 3.70-3.55 (1H, m), 2.91 (2H, q, J=7.4 Hz), 2.45-2.35 (1H, m), 2.25-2.15 (1H, m), 2.00-1.90 (1H, m), 1.40 (3H, t, J=7.4 Hz), 1.40-1.30 (1H, m), 1.20-1.10 (1H, m), 0.91 (3H, t, J=7.2 Hz), 0.87-0.77 (1H, m), 0.54-0.44 (2H, m), 0.25-0.15 (1H, m). MS (NH₃-CI): m/e calc'd for C₂₂H₂₆F₃N₄O: 419.2057, found 419.2058; 421 (3), 420 (25), 419 (100).

Example 1153 spectral data: TLC R_(F) 0.48 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.00 (1H, s), 7.89 (1H, d, J=8.0 Hz), 7.84 (1H, s), 7.69 (1H, d, J=8.0 Hz), 7.40-7.30 (5H, m), 5.14 (1H, d, J=10.2 Hz), 2.82 (1H, dq, J=15.5, 7.7 Hz), 2.68 (1H, dq, J=15.5, 7.7 Hz), 2.15 (1H, br), 1.23 (3H, t, J=7.7 Hz), 1.13-1.03 (1H, m), 0.78-0.62 (2H, m), 0.53-0.43 (1H, m). MS (NH₃-CI): m/e calculated for C₂₄H₂₁ClF₃N₄: 457.1407, found 457.1389; 460 (9), 459 (35), 458 (29), 457 (100).

Example 1155 spectral data: TLC R_(F) 0.46 (25:75 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.98 (1H, s), 7.83 (1H, d, J=8.4 Hz), 7.46-7.27 (7H, m), 5.13 (1H, d, J=10.7 Hz), 2.88-2.62 (2H, m), 2.15 (1H, br), 1.26 (3H, t, J=7.5 Hz), 1.12-1.02 (1H, m), 0.78-0.62 (2H, m), 0.54-0.44 (1H, m). MS (NH₃-CI): m/e calculated for C₂₄H₂₁ClF₃N₄O: 473.1361, found 473.1365; 476 (9), 475 (36), 474 (29), 473 (100).

Example 1157 spectral data: TLC R_(F) 0.19 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.93 (1H, s), 7.77 (1H, d, J=8.8 Hz), 7.40-7.30 (6H, m), 7.19 (1H, dd, J=8.8, 2.2 Hz), 5.13 (1H, d, J=10.6 Hz), 3.92 (3H, s), 2.79 (1H, dq, J=15, 7.7 Hz), 2.64 (1H, dq, J=15, 7.7 Hz), 2.12 (1H, br), 1.21 (3H, t, J=7.7 Hz), 1.10-1.00 (1H, m), 0.77-0.62 (2H, m), 0.55-0.45 (1H, m). MS (NH₃-CI): m/e calc'd for C₂₅H₂₄F₃N₄O: 453.1902, found 453.1903; 455 (4), 454 (28), 453 (100).

Example 1158 spectral data: TLC R_(F) 0.16 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.98 (1H, s), 7.46-7.25 (7H, m), 5.12 (1H, br d, J=9 Hz), 2.85-2.62 (2H, m), 2.14 (1H, br), 2.13 (3H, d, J=0.7 Hz), 1.18 (3H, dq, J=7.7, 4.1 Hz), 0.75-0.35 (4H, m). MS (NH₃-CI): m/e calc'd for C₂₄H₂₃Cl₂N₄: 437.1300, found 437.1294; 440 (19), 439 (67), 438 (32), 437 (100).

Example 1161 spectral data: MS (NH₃-CI): m/e 441 (M+H⁺, 100%).

Example 1163 spectral data: TLC R_(F) 0.44 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.00 (1H, s), 7.89 (1H, d, J=8.4 Hz), 7.84 (1H, s), 7.69 (1H, d, J=8.4 Hz), 7.38 (2H, d, J=9 Hz), 7.05 (2H, d, J=9 Hz), 5.08 (1H, d, J=10.2 Hz), 2.82 (1H, dq, J=15.5, 7.7 Hz), 2.68 (1H, dq, J=15.5, 7.7 Hz), 2.14 (1H, m), 1.25 (3H, t, J=7.7 Hz), 1.10-1.01 (1H, m), 0.74-0.62 (2H, m), 0.51-0.41 (1H, m). MS (NH₃-CI): m/e calculated for C₂₄H₂₀ClF₄N₄: 475.1313, found 475.1307; 479 (1), 478 (9), 477 (35), 476 (30), 475 (100).

Example 1222 spectral data: MS (NH₃-CI): m/e 363 (M+H⁺, 100%).

Example 1252 spectral data: TLC R_(F) 0.24 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.72 (1H, s), 7.87 (1H, dd, J=8.8, 5.5 Hz), 7.46 (1H, dd, J=8.8, 2.5 Hz), 7.35-7.26 (1H, m), 7.24-7.18 (6H, m), 7.08-7.01 (4H, m), 4.89-4.79 (1H, m), 4.49 (2H, d, J=12.1 Hz), 4.37 (2H, d, J=12.1 Hz), 4.27 (2H, t, J=9.3 Hz), 4.01 (2H, dd, J=9.9, 5.2 Hz), 2.98 (2H, q, J=7.7 Hz), 1.39 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e calc'd for C₃₁H₂₉F₄N₄O₂: 565.2227, found 565.2226; 567 (7), 566 (36), 565 (100).

Example 1255 spectral data: TLC R_(F) 0.50 (25:75 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.80 (1H, d, J=8.4 Hz), 7.45-7.43 (1H, m), 7.31-7.27 (1H, dm, J=8 Hz), 3.80-3.73 (1H, m), 2.93 (2H, q, J=7.3 Hz), 2.40 (1H, br), 2.25-2.14 (1H, m), 1.95 (1H, br), 1.42 (3H, t, J=7.5 Hz), 1.35-1.10 (2H, m), 0.92 (3H, t, J=7.3 Hz), 0.91-0.80 (1H, m), 0.53-0.44 (2H, m), 0.24-0.14 (1H, m). MS (NH₃-CI): m/e calculated for C₂₁H₂₃ClF₃N₄O: 439.1519, found 439.1524; 442 (8), 441 (34), 440 (26), 439 (100).

Example 1256 spectral data: TLC R_(F) 0.48 (25:75 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.95 (1H, s), 7.79 (1H, d, J=8.4 Hz), 7.45-7.43 (1H, m), 7.27 (1H, dm, J=8 Hz), 4.35-4.25 (1H, m), 2.96 (2H, q, J=7.4 Hz), 2.42 (2H, br), 2.12-1.93 (2H, m), 1.43 (3H, t, J=7.4 Hz), 1.37-1.22 (2H, m), 0.91 (3H, t, J=7.2 Hz), 0.83 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calculated for C₂₀H₂₃ClF₃N₄O: 427.1514, found 427.1515; 430 (8), 429 (34), 428 (25), 427 (100).

Example 1295 spectral data: TLC R_(F) 0.37 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.38 (1H, s), 6.83 (1H, s), 4.46 (1H, m, J=7.3 Hz), 3.94 (3H, s), 3.91 (3H, s), 2.96 (2H, q, J=7.6 Hz), 2.49-2.39 (1H, m), 2.43 (3H, s), 2.12-2.02 (1H, m), 1.75 (3H, d, J=6.5 Hz), 1.44 (3H, t, J=7.5 Hz), 0.86 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₂₀H₂₇N₄O₂: 355.2134, found 355.2139; 357 (3), 356 (23), 355 (100).

Example 1296 spectral data: TLC R_(F) 0.37 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.00 (1H, s), 7.68 (1H, d, J=8.4 Hz), 7.57 (1H, d, J=2.2 Hz), 7.39 (1H, dd, J=8.4, 2.2 Hz), 7.27 (2H, d, J=8.4 Hz), 6.69 (2H, d, J=8.4 Hz), 5.56 (1H, dd, J=9.7, 7.4 Hz), 3.79 (3H, s), 2.92-2.75 (3H, m), 2.65-2.55 (1H, m), 1.31 (3H, t, J=7.5 Hz), 0.92 (3H, t, J=6.6 Hz). MS (NH₃-CI): m/e calc'd for C₂₃H₂₃Cl₂N₄O: 441.1249, found 441.1247; 445 (12), 444 (18), 443 (67), 442 (30), 441 (100).

Example 1319 spectral data: MS (NH₃-CI): m/e 459 (M+H⁺, 100%).

Example 1320 spectral data: ¹H NMR (300 MHz, CDCl₃): δ8.99 (s, 1H), 7.68 (d, 1H, J=8.4 Hz), 7.58 (d, 1H, J=1.9 Hz), 7.42-7.3 (m, 6H), 6.04 (q, 1H), 2.82, (m, 2H), 2.16 (d, 3H, J=7.4 Hz), 1.27 (t, 3H, J=7.3, 7.7 Hz).

Example 1321 7906-5 spectral data: ¹H NMR (300 MHz, CDCl₃): δ9.02 (s, 1H), 7.98 (d, 1H), 7.71 (d, 1H), 7.57 (d, 1H), 7.42-7.26 (m, 3H), 7.15 (m, 1H), 5.38 (d, 1H), 2.65 (m, 1H), 2.4 (m, 1H), 1.85 (m, 1H), 1.82 (s, 3H), 0.97 (t, 3H), 0.8 (m, 2H), 0.6 (m, 2H).

Example 1322 spectral data: MS (NH₃-CI): m/e 437 (M+H⁺, 100%).

Example 1323 spectral data: MS (NH₃-CI): m/e 455 (M+H⁺, 100%).

Example 1324 spectral data: MS (ESI): m/e 425 (M+H⁺), 381 (M+H⁺—CO₂, 100%).

Example 1325 spectral data: MS (NH₃-CI): m/e 413 (M+H⁺, 100%).

Example 1326 spectral data: MS (NH₃-CI): m/e 427 (M+H⁺, 100%).

Example 1327 spectral data: MS (NH₃-CI): m/e 427 (M+H⁺, 100%).

Example 1328 spectral data: MS (NH₃-CI): m/e 427 (M+H⁺, 100%).

Example 1329 spectral data: MS (NH₃-CI): m/e 423 (M+H⁺, 100%).

Example 1330 spectral data: MS (NH₃-CI): m/e 418 (M+H⁺, 100%).

Example 1331 spectral data: MS (NH₃-CI): m/e 418 (M+H⁺, 100%).

Example 1332 spectral data: MS (NH₃-CI): m/e 499 (M+H⁺, 100%).

Example 1333 spectral data: MS (NH₃-CI): m/e 453 (M+H⁺, 100%).

Example 1334 spectral data: MS (NH₃-CI): m/e 423 (M+H⁺, 100%).

Example 1335 spectral data: MS (NH₃-CI): m/e 372 (M+H⁺, 100%).

Example 1337 spectral data: MS (NH₃-CI): m/e 443 (M+H⁺, 100%).

Example 1338 spectral data: MS (NH₃-CI): m/e 427 (M+H⁺, 100%).

Example 1339 spectral data: MS (NH₃-CI): m/e 379 (M+H⁺, 100%).

Example 1341 spectral data: MS (NH₃-CI): m/e 393 (M+H⁺, 100%).

Example 1342 spectral data: MS (NH₃-CI): m/e 378 (M+H⁺, 100%).

Example 1343 spectral data: MS (NH₃-CI): m/e 346 (M+H⁺, 100%).

Example 1344 spectral data: MS (NH₃-CI): m/e 363 (M+H⁺, 100%).

Example 1346 spectral data: MS (NH₃-CI): m/e 416 (M+H⁺, 100%).

Example 1370 spectral data: TLC R_(F) 0.23 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.89 (1H, s), 7.72 (1H, d, J=8.4 Hz), 7.35 (1H, d, J=2.5 Hz), 7.17 (1H, dd, J=8.4, 2.5 Hz), 4.27 (1H, br), 3.91 (3H, s), 2.93 (2H, q, J=7.7 Hz), 2.40 (2H, br), 2.10-1.95 (2H, m), 1.41 (3H, t, J=7.7 Hz), 1.39-1.27 (1H, m), 1.20-1.07 (1H, m), 0.91 (3H, t, J=7.3 Hz), 0.81 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₂₁H₂₆F₃N₄O: 407.2058, found 407.2052; 409 (3), 408 (24), 407 (100).

Example 1371 spectral data: MS (ESI): m/e 377 (M+2), 375 (M⁺, 100 %).

(b) Q1=2-tetrazolyl

(c) Q2=1,2,4-triazol-2-yl

TABLE 1A

(A)

(B)

(C) Ex. mp, No. R² X R³ R⁴ R¹² R¹¹ R⁶ R^(1a) R^(1b) ° C.^(a) 1043 CH₃ CH₂ H CH₃ CH₃ CH₃ H CH₃ C₃H₇ oil

Key:

(a) Where the compound is indicated as an “oil” data is provided below:

Example 1043 spectral data: TLC R_(F) 0.40 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.91 (1H, s), 7.43 (1H s), 7.10 (1H, s), 4.60-4.50 (1H, m), 2.94 (2H, dq, J=7.5, 2.0 Hz), 2.45-2.35 (1H, m), 2.35 (3H, s), 2.28 (6H, s), 2.07-1.97 (1H, m), 1.73 (3H, d, J=6.9 Hz), 1.41 (3H, t, J=7.5 Hz), 1.40-1.27 (1H, m), 1.20-1.07 (1H, m), 0.92 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₁H₂₉N₄: 337.2392, found 337.2396; 339 (3), 338 (23), 337 (100). Analysis calc'd for C₂₁H₂₈N₄: C, 74.96; H, 8.40; N, 16.65; found: C, 74.28; H, 8.02; N, 16.37.

TABLE 1B

(A)

(B)

(C) Ex. No. R² X R⁴ R⁵ R^(1a) R^(1b) mp, ° C.^(a) 1270 CH₃ CH₂ CF₃ O(CH₂)₂— c-C₃H₅ c-C₃H₅ — OH 1271 CH₃ CH₂ CF₃ OCH₂CO₂— c-C₃H₅ c-C₃H₅ — C₂H₅ 1272 CH₃ CH₂ CF₃ OCH₂CO— c-C₃H₅ c-C₃H₅ — N(CH₃)₂ 1273 CH₃ CH₂ CF₃ O(CH₂)₂— c-C₃H₅ c-C₃H₅ — NMe₃ ⁺Cl⁻ 1274 CH₃ CH₂ CF₃ OCH₂CH— c-C₃H₅ c-C₃H₅ — (OH)C₂H₅ 1275 CH₃ CH₂ OCH₂OCH₃ CH₃ CH₃ C₃H₇ 77-79 1276 CH₃ CH₂ OH CH₃ CH₃ C₃H₇ — 1277 CH₃ CH₂ OC₂H₅ CH₃ CH₃ C₃H₇ — 1278 CH₃ CH₂ OC₃H₇ CH₃ CH₃ C₃H₇ — 1279 CH₃ CH₂ O(CH₂)₂— CH₃ CH₃ C₃H₇ — OH 1280 CH₃ CH₂ OCH₂CO₂— CH₃ CH₃ C₃H₇ — C₂H₅ 1281 CH₃ CH₂ OCH₂CO— CH₃ CH₃ C₃H₇ — N(CH₃)₂ 1282 CH₃ CH₂ O(CH₂)₂— CH₃ CH₃ C₃H₇ — NMe₃ ⁺Cl⁻ 1283 CH₃ CH₂ OCH₂CH— CH₃ CH₃ C₃H₇ — (OH)C₂H₅

TABLE 1C

Ex. mp, No. X R⁴ R⁵ R¹¹ R^(1a) R^(1b) ° C. 1501 CH₂ Cl CF₃ H C₃H₇ OCH₃ 76-78 1502 CH₂ Cl CF₃ H C₂H₅ C₂H₄OCH₃ oil 1503 CH₂ Cl Cl H C₂H₅ C₂H₄OCH₃ — 1504 CH₂ Cl OCH₃ H C₂H₅ C₂H₄OCH₃ — 1505 CH₂ CF₃ OCH₃ H C₂H₅ C₂H₄OCH₃ — 1506 CH₂ Cl SO₂CH₃ H C₂H₅ C₂H₄OCH₃ — 1507 CH₂ Cl COCH₃ H C₂H₅ C₂H₄OCH₃ — 1508 CH₂ CH₃ OCH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1509 CH₂ Cl CH₃ F C₂H₅ C₂H₄OCH₃ — 1510 CH₂ CH₃ OCH₃ F C₂H₅ C₂H₄OCH₃ — 1511 CH₂ CH₃ CH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1512 CH₂ Cl CF₃ H c-C₃H₅ C₂H₄OCH₃ — 1513 CH₂ Cl Cl H c-C₃H₅ C₂H₄OCH₃ — 1514 CH₂ Cl OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1515 CH₂ CF₃ OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1516 CH₂ Cl SO₂CH₃ H c-C₃H₅ C₂H₄OCH₃ — 1517 CH₂ Cl COCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1518 CH₂ CH₃ OCH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1519 CH₂ Cl CH₃ F c-C₃H₅ C₂H₄OCH₃ — 1520 CH₂ CH₃ OCH₃ F c-C₃H₅ C₂H₄OCH₃ — 1521 CH₂ CH₃ CH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1522 CH₂ Cl CF₃ H C₂H₅ CH₂OCH₃ oil 1523 CH₂ Cl Cl H C₂H₅ CH₂OCH₃ — 1524 CH₂ Cl OCH₃ H C₂H₅ CH₂OCH₃ — 1525 CH₂ CF₃ OCH₃ H C₂H₅ CH₂OCH₃ — 1526 CH₂ Cl SO₂CH₃ H C₂H₅ CH₂OCH₃ — 1527 CH₂ Cl COCH₃ H C₂H₅ CH₂OCH₃ — 1528 CH₂ CH₃ OCH₃ CH₃ C₂H₅ CH₂OCH₃ — 1529 CH₂ Cl CH₃ F C₂H₅ CH₂OCH₃ — 1530 CH₂ CH₃ OCH₃ F C₂H₅ CH₂OCH₃ — 1531 CH₂ CH₃ CH₃ CH₃ C₂H₅ CH₂OCH₃ — 1532 CH₂ Cl CF₃ H c-C₃H₅ CH₂OCH₃ — 1533 CH₂ Cl Cl H c-C₃H₅ CH₂OCH₃ — 1534 CH₂ Cl OCH₃ H c-C₃H₅ CH₂OCH₃ — 1535 CH₂ CF₃ OCH₃ H c-C₃H₅ CH₂OCH₃ — 1536 CH₂ Cl SO₂CH₃ H c-C₃H₅ CH₂OCH₃ — 1537 CH₂ Cl COCH₃ H c-C₃H₅ CH₂OCH₃ — 1538 CH₂ CH₃ OCH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1539 CH₂ Cl CH₃ F c-C₃H₅ CH₂OCH₃ — 1540 CH₂ CH₃ OCH₃ F c-C₃H₅ CH₂OCH₃ — 1541 CH₂ CH₃ CH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1542 O Cl CF₃ H C₂H₅ C₂H₄OCH₃ oil 1543 O Cl Cl H C₂H₅ C₂H₄OCH₃ — 1544 O Cl OCH₃ H C₂H₅ C₂H₄OCH₃ — 1545 O CF₃ OCH₃ H C₂H₅ C₂H₄OCH₃ — 1546 O Cl SO₂CH₃ H C₂H₅ C₂H₄OCH₃ — 1547 O Cl COCH₃ H C₂H₅ C₂H₄OCH₃ — 1548 O CH₃ OCH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1549 O Cl CH₃ F C₂H₅ C₂H₄OCH₃ — 1550 O CH₃ OCH₃ F C₂H₅ C₂H₄OCH₃ — 1551 O CH₃ CH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1552 O Cl CF₃ H c-C₃H₅ C₂H₄OCH₃ — 1553 O Cl Cl H c-C₃H₅ C₂H₄OCH₃ — 1554 O Cl OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1555 O CF₃ OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1556 O Cl SO₂CH₃ H c-C₃H₅ C₂H₄OCH₃ — 1557 O Cl COCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1558 O CH₃ OCH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1559 O Cl CH₃ F c-C₃H₅ C₂H₄OCH₃ — 1560 O CH₃ OCH₃ F c-C₃H₅ C₂H₄OCH₃ — 1561 O CH₃ CH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1562 O Cl CF₃ H C₂H₅ CH₂OCH₃ oil 1563 O Cl OCH₃ H C₂H₅ CH₂OCH₃ — 1564 O CF₃ OCH₃ H C₂H₅ CH₂OCH₃ — 1565 O Cl SO₂CH₃ H C_(2H) ₅ CH₂OCH₃ — 1566 O Cl COCH₃ H C₂H₅ CH₂OCH₃ — 1567 O CH₃ OCH₃ CH₃ C₂H₅ CH₂OCH₃ — 1568 O Cl CH₃ F C₂H₅ CH₂OCH₃ — 1569 O CH₃ OCH₃ F C₂H₅ CH₂OCH₃ — 1570 O CH₃ CH₃ CH₃ C₂H₅ CH₂OCH₃ — 1571 O Cl CF₃ H c-C₃H₅ CH₂OCH₃ — 1572 O Cl Cl H c-C₃H₅ CH₂OCH₃ — 1573 O Cl OCH₃ H c-C₃H₅ CH₂OCH₃ — 1574 O CF₃ OCH₃ H c-C₃H₅ CH₂OCH₃ — 1575 O Cl SO₂CH₃ H c-C₃H₅ CH₂OCH₃ — 1576 O Cl COCH₃ H c-C₃H₅ CH₂OCH₃ — 1577 O CH₃ OCH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1578 O Cl CH₃ F c-C₃H₅ CH₂OCH₃ — 1579 O CH₃ OCH₃ F c-C₃H₅ CH₂OCH₃ — 1580 O CH₃ CH₃ CH₃ c-C₃H₅ CH₂OCH₃ —

TABLE 1D

Ex. mp, No. X R⁴ R⁵ R¹¹ R^(1a) R^(1b) ° C. 1601 CH₂ CH₃ Cl H C₂H₅ c-C₃H₅ 109- 111 1602 CH₂ Cl Cl H C₂H₅ C₂H₄OCH₃ — 1603 CH₂ Cl OCH₃ H C₂H₅ C₂H₄OCH₃ — 1604 CH₂ CF₃ OCH₃ H C₂H₅ C₂H₄OCH₃ — 1605 CH₂ Cl SO₂CH₃ H C₂H₅ C₂H₄OCH₃ — 1606 CH₂ Cl COCH₃ H C₂H₅ C₂H₄OCH₃ — 1607 CH₂ CH₃ OCH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1608 CH₂ Cl CH₃ F C₂H₅ C₂H₄OCH₃ — 1609 CH₂ CH₃ OCH₃ F C₂H₅ C₂H₄OCH₃ — 1610 CH₂ CH₃ CH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1611 CH₂ Cl CF₃ H c-C₃H₅ C₂H₄OCH₃ — 1612 CH₂ Cl Cl H c-C₃H₅ C₂H₄OCH₃ — 1613 CH₂ Cl OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1614 CH₂ CF₃ OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1615 CH₂ Cl SO₂CH₃ H c-C₃H₅ C₂H₄OCH₃ — 1616 CH₂ Cl COCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1617 CH₂ CH₃ OCH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1618 CH₂ Cl CH₃ F c-C₃H₅ C₂H₄OCH₃ — 1619 CH₂ CH₃ OCH₃ F c-C₃H₅ C₂H₄OCH₃ — 1620 CH₂ CH₃ CH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1621 CH₂ Cl CF₃ H C₂H₅ CH₂OCH₃ oil 1622 CH₂ Cl Cl H C₂H₅ CH₂OCH₃ — 1623 CH₂ Cl OCH₃ H C₂H₅ CH₂OCH₃ — 1624 CH₂ CF₃ OCH₃ H C₂H₅ CH₂OCH₃ — 1625 CH₂ Cl SO₂CH₃ H C₂H₅ CH₂OCH₃ — 1626 CH₂ Cl COCH₃ H C₂H₅ CH₂OCH₃ — 1627 CH₂ CH₃ OCH₃ CH₃ C₂H₅ CH₂OCH₃ — 1628 CH₂ Cl CH₃ F C₂H₅ CH₂OCH₃ — 1629 CH₂ CH₃ OCH₃ F C₂H₅ CH₂OCH₃ — 1630 CH₂ CH₃ CH₃ CH₃ C₂H₅ CH₂OCH₃ — 1631 CH₂ Cl CF₃ H c-C₃H₅ CH₂OCH₃ — 1632 CH₂ Cl Cl H c-C₃H₅ CH₂OCH₃ — 1633 CH₂ Cl OCH₃ H c-C₃H₅ CH₂OCH₃ — 1634 CH₂ CF₃ OCH₃ H c-C₃H₅ CH₂OCH₃ — 1635 CH₂ Cl SO₂CH₃ H c-C₃H₅ CH₂OCH₃ — 1636 CH₂ Cl COCH₃ H c-C₃H₅ CH₂OCH₃ — 1637 CH₂ CH₃ OCH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1638 CH₂ Cl CH₃ F c-C₃H₅ CH₂OCH₃ — 1639 CH₂ CH₃ OCH₃ F c-C₃H₅ CH₂OCH₃ — 1640 CH₂ CH₃ CH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1641 O Cl CF₃ H C₂H₅ C₂H₄OCH₃ oil 1642 O Cl Cl H C₂H₅ C₂H₄OCH₃ — 1643 O Cl OCH₃ H C₂H₅ C₂H₄OCH₃ — 1644 O CF₃ OCH₃ H C₂H₅ C₂H₄OCH₃ — 1645 O Cl SO₂CH₃ H C₂H₅ C₂H₄OCH₃ — 1646 O Cl COCH₃ H C₂H₅ C₂H₄OCH₃ — 1647 O CH₃ OCH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1648 O Cl CH₃ F C₂H₅ C₂H₄OCH₃ — 1649 O CH₃ OCH₃ F C₂H₅ C₂H₄OCH₃ — 1650 O CH₃ CH₃ CH₃ C₂H₅ C₂H₄OCH₃ — 1651 O Cl CF₃ H c-C₃H₅ C₂H₄OCH₃ — 1652 O Cl Cl H c-C₃H₅ C₂H₄OCH₃ — 1653 O Cl OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1654 O CF₃ OCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1655 O Cl SO₂CH₃ H c-C₃H₅ C₂H₄OCH₃ — 1656 O Cl COCH₃ H c-C₃H₅ C₂H₄OCH₃ — 1657 O CH₃ OCH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1658 O Cl CH₃ F c-C₃H₅ C₂H₄OCH₃ — 1659 O CH₃ OCH₃ F c-C₃H₅ C₂H₄OCH₃ — 1660 O CH₃ CH₃ CH₃ c-C₃H₅ C₂H₄OCH₃ — 1661 O Cl CF₃ H C₂H₅ CH₂OCH₃ oil 1662 O Cl OCH₃ H C₂H₅ CH₂OCH₃ — 1663 O CF₃ OCH₃ H C₂H₅ CH₂OCH₃ — 1664 O Cl SO₂CH₃ H C₂H₅ CH₂OCH₃ — 1665 O Cl COCH₃ H C₂H₅ CH₂OCH₃ — 1666 O CH₃ OCH₃ CH₃ C₂H₅ CH₂OCH₃ — 1667 O Cl CH₃ F C₂H₅ CH₂OCH₃ — 1668 O CH₃ OCH₃ F C₂H₅ CH₂OCH₃ — 1669 O CH₃ CH₃ CH₃ C₂H₅ CH₂OCH₃ — 1670 O Cl CF₃ H c-C₃H₅ CH₂OCH₃ — 1671 O Cl Cl H c-C₃H₅ CH₂OCH₃ — 1672 O Cl OCH₃ H c-C₃H₅ CH₂OCH₃ — 1673 O CF₃ OCH₃ H c-C₃H₅ CH₂OCH₃ — 1674 O Cl SO₂CH₃ H c-C₃H₅ CH₂OCH₃ — 1675 O Cl COCH₃ H c-C₃H₅ CH₂OCH₃ — 1676 O CH₃ OCH₃ CH₃ c-C₃H₅ CH₂OCH₃ — 1677 O Cl CH₃ F c-C₃H₅ CH₂OCH₃ — 1678 O CH₃ OCH₃ F c-C₃H₅ CH₂OCH₃ — 1679 O CH₃ CH₃ CH₃ c-C₃H₅ CH₂OCH₃ —

The methods discussed below in the preparation of 1-benzyl-6-methyl-4-(2,4,6-trimethylphenyl)imidazo[4,5-c]pyridine (Example 2001, Table 2, Structure A) may be used to prepare all of the examples of Structure A contained in Table 2, with minor procedural modifications where necessary and use of reagents of the appropriate structure.

The methods of Schemes 13 and 14 may be used to prepare many of the examples of Structure B and Structure C contained in Table 2, with minor procedural modifications where necessary and use of reagents of the appropriate structure.

EXAMPLE 2001 Preparation of 1-benzyl-6-methyl-4-(2,4,6-trimethylphenyl)imidazo[4,5-c]pyridine

Part A. A solution of 4-chloro-6-methyl-3-nitropyridone (5.0 g, 26.5 mmol) in acetonitrile (93 mL) was treated with benzylamine (2.89 mL, 26.5 mmol) and diisopropylethylamine (5.54 mL, 31.8 mmol). The mixture was heated to reflux for 4 hrs., then cooled to ambient temperature and allowed to stir for 12 hrs. The mixture was partitioned between dichloromethane and water (200 mL each), and the aqueous layer was extracted with dichloromethane (200 mL). The extracts were washed in sequence with water (200 mL) and combined, and the resulting precipitate was collected by filtration. The filtrate was dried over sodium sulfate, refiltered and evaporated to afford a second crop of crystalline product, 4-benzylamino-6-methyl-3-nitropyridone (6.74 g total, 26.0 mmol, 98%). m.p. 246-247° C. TLC R_(F) 0.35 (10:90 isopropanol-ethyl acetate). ¹H NMR (300 MHz, CDCl₃): d 10.48 (1H, br s), 9.69 (1H, br s), 7.41-7.26 (5H, m), 5.66 (1H, s), 4.57 (2H, d, J=5.5 Hz), 2.26 (3H, s). MS (NH₃-CI): m/e 261 (10), 260 (70), 226 (100).

Part B. A solution of the pyridone from Part A (6.72 g, 25.9 mmol) in phosphorus oxychloride (52 mL, 25.5 mmol) was stirred at ambient temperature for 3 d. The reaction mixture was poured into a mixture of ice (150 g) and dichloromethane (200 mL). After the ice had melted, 100 mL more dichloromethane was added, and the pH of the mixture was adjusted to 7 with solid NaHCO₃. The mixture was separated, and the aqueous phase was extracted with dichloromethane. The extracts were combined, dried over sodium sulfate, filtered and evaporated to afford the product (4-benzylamino-2-chloro-6-methyl-3-nitropyridine) as a bright yellow crystalline solid (6.45 g, 23.2 mmol, 90%). TLC R_(F) 0.76 (ethyl acetate). ¹H NMR (300 MHz, CDCl₃): d 7.43-7.26 (5H, m), 7.04 (1H, br), 6.47 (1H, s), 4.48 (2H, d, J=5.5 Hz), 2.40 (3H, s). MS (NH₃-CI): m/e 281 (5), 280 (35), 279 (17), 278 (100).

Part C. A solution of the nitro compound from Part B above (6.42 g, 23.1 mmol) in methanol (162 mL) was treated with iron powder (13.61 g) and glacial acetic acid (13.6 mL). The resulting mixture was heated to reflux for 2 h, then cooled, filtered through celite (with methanol washing) and evaporated. The residual material was taken up in dichloromethane (231 mL) and 1 N aq. HCl (162 mL), and adjusted to neutral pH by addition of solid NaHCO₃. This mixture was filtered through celite and separated, and the aqueous phase was extracted with dichloromethane. The extracts were combined, dried over Na₂SO₄, filtered and evaporated to afford the product, 3-amino-4-benzylamino-2-chloro-6-methylpyridine, as a solid (5.59 g, 22.6 mmol, 98%). m.p. 177-178° C. TLC R_(F) 0.60 (ethyl acetate). ¹H NMR (300 MHz, CDCl₃): d 7.41-7.32 (5H, m), 6.33 (1H, s), 4.54 (1H, br), 4.36 (2H, d, J=5.1 Hz), 3.30 (2H, br s), 2.35 (3H, s). MS (NH₃-CI): m/e 251 (6), 250 (37), 249 (19), 248 (100).

Part D. A suspension of the diamine from Part C above (2.15 g, 8.68 mmol) in triethyl orthopropionate (5 mL) was treated with conc. HCl (3 drops), and heated to reflux for 1 h, then cooled and the excess orthoester removed by vacuum distillation. The pot residue was taken up in ethyl acetate (120 mL), which was washed with water and brine (100 mL each). The aqueous phases were back-extracted in sequence with ethyl acetate, and the extracts were combined, dried over Na₂SO₄, filtered and evaporated to afford N-(4-benzylamino-2-chloro-6-methylpyridin-3-yl)propionamide O-ethyl imidate (2.62 g, 91%). TLC R_(F) 0.40 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.39-7.29 (5H, m), 6.29 (1H, s), 4.64 (1H, br t, J=5.8 Hz), 4.37 (2H, d, J=5.8 Hz), 4.25 (2H, br), 2.35 (3H, s), 2.18-2.11 (2H, m), 1.36 (3H, t, J=7.0 Hz), 1.06 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e 335 (7), 334 (34), 333 (22), 332 (100).

Part E. A solution of the compound from Part D (2.62 g, 7.90 mmol) in phenyl ether (10 mL) was heated to 170° C. for 6 h, then cooled and poured into ethyl acetate (150 mL). This was washed with water and brine (100 mL each), then dried over Na₂SO₄, filtered and evaporated. The residual liquid was separated by column chromatography (hexane, then ethyl acetate) to afford the product, 1-benzyl-4-chloro-2-ethyl-6-methylimidazo[4,5-c]pyridine, as an oil (2.16 g, 96%). m.p. 140-141° C. TLC R_(F) 0.06 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.36-7.32 (3H, m), 7.02-6.98 (2H, m), 6.93 (1H, s), 5.31 (2H, s), 2.89 (2H, q, J=7.3 Hz), 2.58 (3H, s), 1.39 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e 289 (6), 288 (35), 287 (20), 286 (100).

Part F. A solution of zinc chloride (538 mg) in tetrahydrofuran (7 mL) was treated with a tetrahydrofuran solution of 2-mesitylmagnesium bromide (3.95 mL, 1.0 M), and stirred for 1 h. In another flask, a solution of bis(triphenylphosphine)palladium chloride (93 mg, 0.132 mmol) in tetrahydrofuran (5 mL) was treated with a hexane solution of diisobutylaluminum hydride (0.263 mL, 1.0 M), and this solution was stirred for 20 min. The arylzinc solution was then delivered by cannula to the flask containing the palladium catalyst, which was followed by the chloride prepared in Part E. The mixture was heated to reflux for 12 h, then cooled, and poured into water (100 mL). This was extracted with ethyl acetate (2×150 mL), and the extracts were washed with brine, combined, dried over Na₂SO₄, filtered and evaporated. The residual material was separated by column chromatography (1:1 ethyl acetate-hexane) to afford the title product as a solid, recrystallized to purity from ether (187 mg, 29%). m.p. 177-180° C. (ether). TLC R_(F) 0.27 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.38-7.32 (3H, m), 7.10-7.05 (2H, m), 6.96 (1H, s), 6.93 (2H, s), 5.32 (2H, s), 2.84 (2H, q, J=7.3 Hz), 2.64 (3H, s), 2.30 (3H, s), 2.02 (6H, s), 1.26 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e 372 (4), 371 (29), 370 (100). Analysis calc'd for C₂₅H₂₇N₃: C, 81.26; H, 7.38; N, 11.37; found: C, 80.70; H, 7.26; N, 11.20.

TABLE 2

(A) (B) (C) Ex. No. X R⁴ R⁵ R¹¹ R⁶ R¹ mp, ° C.^(a) 2001 CH₂ Cl Cl H H c-C₄H₇ — 2002 CH₂ Cl Cl H H c-C₅H₉ 111-112 2003 CH₂ Cl Cl H H c-C₆H₁₁ oil 2004 CH₂ Cl Cl H H c-C₇H₁₃ 128-130 2005 CH₃ Cl Cl H H c-C₈H₁₅ — 2006 CH₂ Cl Cl H H 2-CH₃—c-C₅H₈ oil 2007 CH₂ Cl Cl H H 3-CH₃—c-C₅H₈ — 2008 CH₂ Cl Cl H H 2-OCH₃—c-C₅H₈ — 2009 CH₂ Cl Cl H H 2,5-(CH₃)₂—c-C₅H₇ — 2010 CH₂ Cl Cl H H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2011 CH₂ Cl Cl H H 9-fluorenyl oil 2012 CH₂ Cl Cl H H 1-tetrahydronaphthyl oil 2013 CH₂ Cl Cl H H 1-indanyl oil 2014 CH₂ Cl Cl H H 4-chromanyl oil 2015 CH₂ Cl Cl H H 2-oxo-c-C₅H₇ 166-168 2016 CH₂ Cl Cl H H 5-dibenzosubery1 — 2017 CH₂ Cl Cl H H 5-dibenzosuberenyl — 2018 CH₂ Cl CF₃ H H c-C₄H₇ — 2019 CH₂ Cl CF₃ H H c-C₅H₉ 146-147 2020 CH₂ Cl CF₃ H H c-C₆H₁₁ oil 2021 CH₂ Cl CF₃ H H c-C₇H₁₃ 129-130 2022 CH₂ Cl CF₃ H H c-C₈H₁₅ — 2023 CH₂ Cl CF₃ H H 2-CH₃—c-C₅H₈ 98-99 2024 CH₂ Cl CF₃ H H 3-CH₃—c-C₅H₉ — 2025 CH₂ Cl CF₃ H H 2-OCH₃—c-C₅H₉ — 2026 CH₂ Cl CF₃ H H 2,5-(CH₃)₂—c-C₅H₇ — 2027 CH₂ Cl CF₃ H H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2028 CH₂ Cl CF₃ H H 9-fluorenyl — 2029 CH₂ Cl CF₃ H H 1-tetrahydronaphthyl — 2630 CH₂ Cl CF₃ H H 1-indanyl — 2031 CH₂ Cl CF₃ H H 4-chromanyl — 2632 CH₂ Cl CF₃ H H 2-oxo-c-C₅H₇ — 2033 CH₂ Cl CF₃ H H 5-dibenzosuberyl — 2034 CH₂ Cl CF₃ H H 5-dibenzosuberenyl — 2035 CH₂ Cl OCH₃ H H c-C₄H₇ — 2036 CH₂ Cl OCH₃ H H c-C₅H₉ — 2037 CH₂ Cl OCH₃ H H c-C₆H₁₁ — 2038 CH₂ Cl OCH₃ H H c-C₇H₁₃ — 2039 CH₂ Cl OCH₃ H H c-C₈H₁₅ — 2040 CH₂ Cl OCH₃ H H 2-CH₃—c-C₅H₈ — 2041 CH₂ Cl OCH₃ H H 3-CH₃—c-C₅H₉ — 2042 CH₂ Cl OCH₃ H H 2-OCH₃—c-C₅H₈ — 2043 CH₂ Cl OCH₃ H H 2,5-(CH₃)₂—c-C₅H₇ — 2044 CH₂ Cl OCH₃ H H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2045 CH₂ Cl OCH₃ H H 9-fluorenyl — 2046 CH₂ Cl OCH₃ H H 1-tetrahydronaphthyl — 2047 CH₂ Cl OCH₃ H H 1-indanyl — 2048 CH₂ Cl OCH₃ H H 4-chromanyl — 2049 CH₂ Cl OCH₃ H H 2-oxo-c-C₅H₇ — 2050 CH₂ Cl OCH₃ H H 5-dibenzosuberyl — 2051 CH₂ Cl OCH₃ H H 5-dibenzosuberenyl — 2052 CH₂ Cl OCF₃ H H c-C₄H₇ — 2053 CH₂ Cl OCF₃ H H c-C₅H₉ oil 2054 CH₂ Cl OCF₃ H H c-C₆H₁₁ — 2055 CH₂ Cl OCF₃ H H c-C₇H₁₃ — 2056 CH₂ Cl OCF₃ H H c-C₈H₁₅ — 2657 CH₂ Cl OCF₃ H H 2-CH₃—c-C₅H₈ — 2058 CH₂ Cl OCF₃ H H 3-CH₃—c-C₅H₈ — 2059 CH₂ Cl OCF₃ H H 2-OCH₃—c-C₅H₈ — 2060 CH₂ Cl OCF₃ H H 2,5-(CH₃)₂—c-C₅H₇ — 2061 CH₂ Cl OCF₃ H H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2062 CH₂ Cl OCF₃ H H 9-fluorenyl — 2063 CH₂ Cl OCF₃ H H 1-tetrahydronaphthyl — 2064 CH₂ Cl OCF₃ H H 1-indanyl — 2065 CH₂ Cl OCF₃ H H 4-chromanyl — 2066 CH₂ Cl OCF₃ H H 2-oxo-c-C₅H₇ — 2067 CH₂ Cl OCF₃ H H 5-dibenzosuberyl — 2068 CH₂ Cl OCF₃ H H 5-dibenzosuberenyl — 2069 CH₂ Cl CH₃ H H c-C₄H₇ — 2070 CH₂ Cl CH₃ H H c-C₅H₉ — 2071 CH₂ Cl CH₃ H H c-C₆H₁₁ — 2072 CH₂ Cl CH₃ H H c-C₇H₁₃ — 2073 CH₂ Cl CH₃ H H c-C₈H₁₅ — 2074 CH₂ Cl CH₃ H H 2-CH₃—c-C₅H₈ — 2075 CH₂ Cl CH₃ H H 3-CH₃—c-C₅H₈ — 2076 CH₂ Cl CH₃ H H 2-OCH₃—c-C₅H₈ — 2077 CH₂ Cl CH₃ H H 2,5-(CH₃)₂—c-C₅H₇ — 2078 CH₂ Cl CH₃ H H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2079 CH₂ Cl CH₃ H H 9-fluorenyl — 2080 CH₂ Cl CH₃ H H 1-tetrahydronaphthyl — 2081 CH₂ Cl CH₃ H H 1-indanyl — 2082 CH₂ Cl CH₃ H H 4-chromanyl — 2083 CH₂ Cl CH₃ H H 2-oxo-c-C₅H₇ — 2084 CH₂ Cl CH₃ H H 5-dibenzosuberyl — 2085 CH₂ Cl CH₃ H H 5-dibenzosuberenyl — 2086 CH₂ CF₃ Cl H H c-C₄H₇ — 2087 CH₂ CF₃ Cl H H c-C₅H₉ 143-145 2088 CH₂ CF₃ Cl H H c-C₆H₁₁ — 2089 CH₂ CF₃ Cl H H c-C₇H₁₃ — 2090 CH₂ CF₃ Cl H H c-C₈H₁₅ — 2091 CH₂ CF₃ Cl H H 2-CH₃—c-C₅H₈ — 2092 CH₂ CF₃ Cl H H 3-CH₃—c-C₅H₈ — 2093 CH₂ CF₃ Cl H H 2-OCH₃—c-C₅H₈ — 2094 CH₂ CF₃ Cl H H 2,5-(CH₃)₂—c-C₅H₇ — 2095 CH₂ CF₃ Cl H H 2-(CH₃)₂CH—5-CH₃—c-C₆H₈ — 2096 CH₂ CF₃ Cl H H 9-fluorenyl — 2097 CH₂ CF₃ Cl H H 1-tetrahydronaphthyl — 2098 CH₂ CF₃ Cl H H 1-indanyl — 2099 CH₂ CF₃ Cl H H 4-chromanyl — 2100 CH₂ CF₃ Cl H H 2-oxo-c-C₅H₇ — 2101 CH₂ CF₃ Cl H H 5-dibenzosuberyl — 2102 CH₂ CF₃ Cl H H 5-dibenzosuberenyl — 2103 CH₂ CF₃ OCH₃ H H c-C₄H₇ — 2104 CH₂ CF₃ OCH₃ H H c-C₅H₉ 103-106 2105 CH₂ CF₃ OCH₃ H H c-C₆H₁₁ — 2106 CH₂ CF₃ OCH₃ H H c-C₇H₁₃ — 2107 CH₂ CF₃ OCH₃ H H c-C₈H₁₅ — 2108 CH₂ CF₃ OCH₃ H H 2-CH₃—c-C₅H₈ — 2109 CH₂ CF₃ OCH₃ H H 3-CH₃—c-C₅H₈ — 2110 CH₂ CF₃ OCH₃ H H 2-OCH₃—c-C₅H₈ — 2111 CH₂ CF₃ OCH₃ H H 2,5-(CH₃)₂—c-C₅H₇ — 2112 CH₂ CF₃ OCH₃ H H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2113 CH₂ CF₃ OCH₃ H H 9-fluorenyl — 2114 CH₂ CF₃ OCH₃ H H 1-tetrahydronaphthyl — 2115 CH₂ CF₃ OCH₃ H H 1-indanyl — 2116 CH₂ CF₃ OCH₃ H H 4-chromanyl — 2117 CH₂ CF₃ OCH₃ H H 2-oxo-c-C₅H₇ — 2118 CH₂ CF₃ OCH₃ H H 5-dibenzosuberyl — 2119 CH₂ CF₃ OCH₃ H H 5-dibenzosuberenyl — 2120 CH₂ CF₃ F H H c-C₄H₇ — 2121 CH₂ CF₃ F H H c-C₅H₉ — 2122 CH₂ CF₃ F H H c-C₆H₁₁ — 2123 CH₂ CF₃ F H H c-C₇H₁₃ 119-122 2124 CH₂ CF₃ F H H c-C₈H₁₅ — 2125 CH₂ CF₃ F H H 2-CH₃—c-C₅H₈ — 2126 CH₂ CF₃ F H H 3-CH₃—c-C₅H₈ — 2127 CH₂ CF₃ F H H 2-OCH₃—c-C₅H₆ — 2128 CH₂ CF₃ F H H 2,5-(CH₃)₂—c-C₅H₇ — 2129 CH₂ CF₃ F H H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ 155-156 2130 CH₂ CF₃ F H H 9-fluorenyi 184-185 2131 CH₂ CF₃ F H H 1-tetrahydronaphthyl — 2132 CH₂ CF₃ F H H 1-indanyl — 2133 CH₂ CF₃ F H H 4-chromanyl — 2134 CH₂ CF₃ F H H 2-oxo-c-C₅H₇ — 2135 CH₂ CF₃ F H H 5-dibenzosuberyl — 2136 CH₂ CF₃ F H H 5-dibenzosuberenyl — 2137 CH₂ CH₃ OCH₃ CH₃ H c-C₄H₇ — 2138 CH₂ CH₃ OCH₃ CH₃ H c-C₅H₉ — 2139 CH₂ CH₃ OCH₃ CH₃ H c-C₆H₁₁ — 2140 CH₂ CH₃ OCH₃ CH₃ H c-C₇H₁₃ — 2141 CH₂ CH₃ OCH₃ CH₃ H c-C₈H₁₅ — 2142 CH₂ CH₃ OCH₃ CH₃ H 2-CH₃—c-C₅H₈ — 2143 CH₂ CH₃ OCH₃ CH₃ H 3-CH₃—c-C₅H₈ — 2144 CH₂ CH₃ OCH₃ CH₃ H 2-OCH₃—c-C₅H₈ — 2145 CH₂ CH₃ OCH₃ CH₃ H 2,5-(CH₃)₂—c-C₅H₇ — 2146 CH₂ CH₃ OCH₃ CH₃ H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2147 CH₂ CH₃ OCH₃ CH₃ H 9-fluorenyl — 2148 CH₂ CH₃ OCH₃ CH₃ H 1-tetrahydronaphthyl — 2149 CH₂ CH₃ OCH₃ CH₃ H 1-indanyl — 2150 CH₂ CH₃ OCH₃ CH₃ H 4-chromanyl — 2151 CH₂ CH₃ OCH₃ CH₃ H 2-oxo-c-C₅H₇ — 2152 CH₂ CH₃ OCH₃ CH₃ H 5-dibenzosuberyl — 2153 CH₂ CH₃ OCH₃ CH₃ H 5-dibenzosuberenyl — 2154 CH₂ CH₃ OCH₃ Cl H c-C₄H₇ — 2155 CH₂ CH₃ OCH₃ Cl H c-C₅H₉ 115-116 2156 CH₂ CH₃ OCH₃ Cl H c-C₆H₁₁ — 2157 CH₂ CH₃ OCH₃ Cl H c-C₇H₁₃ — 2158 CH₂ CH₃ OCH₃ Cl H c-C₈H₁₅ — 2159 CH₂ CH₃ OCH₃ Cl H 2-CH₃—c-C₅H₈ — 2160 CH₂ CH₃ OCH₃ Cl H 3-CH₃—c-C₅H₈ — 2161 CH₂ CH₃ OCH₃ Cl H 2-OCH₃—c-C₅H₈ — 2162 CH₂ CH₃ OCH₃ Cl H 2,5-(CH₃)₂—c-C₅H₇ — 2163 CH₂ CH₃ OCH₃ Cl H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2164 CH₂ CH₃ OCH₃ Cl H 9-fluorenyl — 2165 CH₂ CH₃ OCH₃ Cl H 1-tetrahydronaphthyl — 2166 CH₂ CH₃ OCH₃ Cl H 1-indanyl — 2167 CH₂ CH₃ OCH₃ Cl H 4-chromanyl — 2168 CH₂ CH₃ OCH₃ Cl H 2-oxo-c-C₅H₇ — 2169 CH₂ CH₃ OCH₃ Cl H 5-dibenzosuberyl — 2170 CH₂ CH₃ OCH₃ Cl H 5-dibenzosuberenyl — 2171 CH₂ CH₃ OCH₃ F H c-C₄H₇ — 2172 CH₂ CH₃ OCH₃ F H c-C₅H₉ — 2173 CH₂ CH₃ OCH₃ F H c-C₆H₁₁ — 2174 CH₂ CH₃ OCH₃ F H c-C₇H₁₃ — 2175 CH₂ CH₃ OCH₃ F H c-C₈H₁₅ — 2176 CH₂ CH₃ OCH₃ F H 2-CH₃—c-C₅H₈ — 2177 CH₂ CH₃ OCH₃ F H 3-CH₃—c-C₅H₈ — 2178 CH₂ CH₃ OCH₃ F H 2-OCH₃—c-C₅H₈ — 2179 CH₂ CH₃ OCH₃ F H 2,5-(CH₃)₂—c-C₅H₇ — 2180 CH₂ CH₃ OCH₃ F H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2181 CH₂ CH₃ OCH₃ F H 9-fluorenyl — 2182 CH₂ CH₃ OCH₃ F H 1-tetrahydronaphthyl — 2183 CH₂ CH₃ OCH₃ F H 1-indanyl — 2184 CH₂ CH₃ OCH₃ F H 4-chromanyl — 2185 CH₂ CH₃ OCH₃ F H 2-oxo-c-C₅H₇ — 2186 CH₂ CH₃ OCH₃ F H 5-dibenzosuberyl — 2187 CH₂ CH₃ OCH₃ F H 5-dibenzosubereryl — 2188 CH₂ CH₃ CH₃ H CH₃ c-C₄H₇ — 2189 CH₂ CH₃ CH₃ H CH₃ c-C₅H₉ — 2190 CH₂ CH₃ CH₃ H CH₃ c-C₆H₁₁ — 2191 CH₂ CH₃ CH₃ H CH₃ c-C₇H₁₃ — 2192 CH₂ CH₃ CH₃ H CH₃ c-C₈H₁₅ — 2193 CH₂ CH₃ CH₃ H CH₃ 2-CH₃—c-C₅H₈ — 2194 CH₂ CH₃ CH₃ H CH₃ 3-CH₃—c-C₅H₈ — 2195 CH₂ CH₃ CH₃ H CH₃ 2-OCH₃—c-C₅H₈ — 2196 CH₂ CH₃ CH₃ H CH₃ 2,5-(CH₃)₂—c-C₅H₇ — 2197 CH₂ CH₃ CH₃ H CH₃ 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2198 CH₂ CH₃ CH₃ H CH₃ 9-fluorenyl — 2199 CH₂ CH₃ CH₃ H CH₃ 1-tetrahydronaphthyl — 2200 CH₂ CH₃ CH₃ H CH₃ 1-indanyl — 2201 CH₂ CH₃ CH₃ H CH₃ 4-chromanyl — 2202 CH₂ CH₃ CH₃ H CH₃ 2-oxo-c-C₅H₇ — 2203 CH₂ CH₃ CH₃ H CH₃ 5-dibenzosuberyl — 2204 CH₂ CH₃ CH₃ H CH₃ 5-dibenzosuberenyl — 2205 CH₂ Cl Cl H CH₃ c-C₄H₇ — 2206 CH₂ Cl Cl H CH₃ c-C₅H₉ — 2207 CH₂ Cl Cl H CH₃ c-C₆H₁₁ — 2208 CH₂ Cl Cl H CH₃ c-C₇H₁₃ — 2209 CH₂ Cl Cl H CH₃ c-C₈H₁₅ — 2210 CH₂ Cl C1 H CH₃ 2-CH₃—c-C₅H₈ — 2211 CH₂ Cl Cl H CH₃ 3-CH₃—c-C₅H₈ — 2212 CH₂ Cl Cl H CH₃ 2-OCH₃—c-C₅H₈ — 2213 CH₂ Cl Cl H CH₃ 2,5-(CH₃)₂—c-C₅H₇ — 2214 CH₂ Cl Cl H CH₃ 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2215 CH₂ Cl Cl H CH₃ 9-fluorenyl — 2216 CH₂ Cl Cl H CH₃ 1-tetrahydronaphthyl oil 2217 CH₂ Cl Cl H CH₃ 1-indanyl — 2218 CH₂ Cl Cl H CH₃ 4-chromanyl — 2219 CH₂ Cl Cl H CH₃ 2-oxo-c-C₅H₇ — 2220 CH₂ Cl Cl H CH₃ 5-dibenzosuberyl — 2221 CH₂ Cl Cl H CH₃ 5-dibenzosuberenyl — 2222 CH₂ CH₃ OCH₃ OCH₃ H c-C₄H₇ — 2223 CH₂ CH₃ OCH₃ OCH₃ H c-C₅H₉ oil 2224 CH₂ CH₃ OCH₃ OCH₃ H c-C₆H₁₁ — 2225 CH₂ CH₃ OCH₃ OCH₃ H c-C₇H₁₃ — 2226 CH₂ CH₃ OCH₃ OCH₃ H c-C₈H₁₅ — 2227 CH₂ CH₃ OCH₃ OCH₃ H 2-CH₃—c-C₅H₈ oil 2228 CH₂ CH₃ OCH₃ OCH₃ H 3-CH₃—c-C₅H₈ — 2229 CH₂ CH₃ OCH₃ OCH₃ H 2-OCH₃—c-C₅H₈ — 2230 CH₂ CH₃ OCH₃ OCH₃ H 2,5-(CH₃)₂—c-C₅H₇ — 2231 CH₂ CH₃ OCH₃ OCH₃ H 2-(CH₃)₂CH—5-CH₃—c-C₆H₉ — 2232 CH₂ CH₃ OCH₃ OCH₃ H 9-fluorenyl — 2233 CH₂ CH₃ OCH₃ OCH₃ H 1-tetrahydronaphthyl — 2234 CH₂ CH₃ OCH₃ OCH₃ H 1-indanyl — 2235 CH₂ CH₃ OCH₃ OCH₃ H 4-chromanyl — 2236 CH₂ CH₃ OCH₃ OCH₃ H 2-oxo-c-C₅H₇ — 2237 CH₂ CH₃ OCH₃ OCH₃ H 5-dibenzosuberyl — 2238 CH₂ CH₃ OCH₃ OCH₃ H 5-dibenzosuberenyl — 2239 O Cl Cl H H c-C₅H₉ — 2240 O Cl CF₃ H H c-C₅H₉ — 2241 O Cl OCH₃ H H c-C₅H₉ — 2242 O Cl OCF₃ H H c-C₅H₉ — 2243 O Cl CH₃ H H c-C₅H₉ — 2244 O CF₃ Cl H H c-C₅H₉ — 2245 O CF₃ OCH₃ H H c-C₅H₉ — 2246 O CH₃ OCH₃ CH₃ H c-C₅H₉ — 2247 O CH₃ OCH₃ Cl H c-C₅H₉ — 2248 O CH₃ OCH₃ F H c-C₅H₉ — 2249 O CH₃ CH₃ H CH₃ c-C₅H₉ — 2250 O Cl Cl H CH₃ c-C₅H₉ —

Key:

a) Where the compound is listed as an “oil”, spectral data is as follows:

Example 2003 spectral data: MS (NH₃-CI): m/e 374 (M+H⁺, 100%).

Example 2006 spectral data: TLC R_(F) 0.20 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.67 (1H, d, J=8.1 Hz), 7.57 (1H, d, J=1.8 Hz), 7.40 (1H, dd, J=8.1, 1.8 Hz), 4.83 (1H, q, J=8.0 Hz), 3.20-3.04 (1H, m), 2.98 (2H, q, J=7.3 Hz), 2.50-2.38 (1H, m), 2.30-2.15 (2H, m), 2.03-1.93 (2H, m), 1.75-1.60 (1H, m), 1.42 (3H, t, J=7.3 Hz), 0.68 (3H, d, J=6.9 Hz). MS (NH₃-CI): m/e calc'd for C₁₉H₂₁Cl₂N₄: 375.1143, found 375.1149; 380 (2), 379 (12), 378 (15), 377 (66), 376 (27), 375 (100).

Example 2011 spectral data: MS (NH₃-CI): m/e 457 (M+H⁺, 100%).

Example 2012 spectral data: TLC R_(F) 0.38 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.72 (1H, d, J=8.5 Hz), 7.58 (1H, d, J=1.8 Hz), 7.47-7.40 (2H, m), 7.24-7.18 (1H, m), 6.56 (1H, d, J=7.7 Hz), 6.18-6.10 (1H, m), 4.82-4.76 (1H, m), 3.15-2.30 (5H, m), 2.10-1.77 (3H, m), 1.27 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₂₃H₂₁Cl₂N₄: 423.1143, found 423.1142; 427 (13), 426 (18), 425 (67), 424 (31), 423 (100).

Example 2013 spectral data: TLC R_(F) 0.28 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.68 (1H, d, J=8.5 Hz), 7.58 (1H, d, J=1.8 Hz), 7.46-7.38 (2H, m), 7.22-7.15 (1H, m), 6.91 (1H, d, J=7.7 Hz), 6.42 (1H, br t, J=7 Hz), 5.30-5.22 (1H, m), 3.43-3.33 (1H, m), 3.20-3.03 (1H, m), 2.89-2.76 (2H, m), 2.56-2.43 (1H, m), 2.01-1.90 (1H, m), 1.31 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₂₂H₁₉Cl₂N₄: 409.0987, found 409.0987; 413 (12), 412 (17), 411 (67), 410 (29), 409 (100).

Example 2014 spectral data: TLC R_(F) 0.38 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.95 (1H, s), 7.71 (1H, d, J=8.4 Hz), 7.59 (1H, d, J=2.2 Hz), 7.42 (1H, dd, J=8.4, 2.2 Hz), 7.26-7.19 (1H, m), 6.98-6.90 (1H, m), 6.58 (1H, d, J=7.7 Hz), 6.30-6.22 (1H, m), 4.60-4.53 (1H, m), 4.43-4.33 (1H, m), 4.20 (1H, br), 2.82-2.72 (1H, m), 2.69-2.58 (1H, m), 2.46-2.36 (1H, m), 2.18-2.08 (1H, m), 1.29 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₂₂H₁₉Cl₂N₄O: 425.0936, found 425.0926; 429 (12), 428 (17), 427 (67), 426 (30), 425 (100).

Example 2020 spectral data: TLC R_(F) 0.43 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.98 (1H, s), 7.81 (2H, d, J=8.4 Hz), 7.67 (1H, dd, J=8.0, 0.7 Hz), 4.26 (1H, m), 3.00 (2H, q, J=7.6 Hz), 2.75-2.66 (2H, m), 2.06-1.90 (4H, m), 1.50-1.36 (4H, m), 1.40 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 412 (7), 411 (34), 410 (25), 409 (100).

Example 2053 spectral data: TLC R_(F) 0.36 (25:75 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.73 (1H, d, J=8.4 Hz), 7.44 (1H, d, J=1.1 Hz), 7.28 (1H, dd, J=8.4, 1.1 Hz), 4.79 (1H, pentet, J=8.4 Hz), 3.01 (2H, q, J=7.7 Hz), 2.62-2.50 (2H, m), 2.23-2.07 (2H, m), 1.89-1.77 (2H, m), 1.66-1.49 (2H, m), 1.41 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e calculated for C₁₉H₁₉ClF₃N₄O: 411.1205, found 411.1208; 414 (7), 413 (34), 412 (24), 411 (100).

Example 2216 spectral data: TLC R_(F) 0.13 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.94 (1H, s), 7.48-7.02 (5H, m), 6.53 (1H, dd, J=7.7, 1.5 Hz), 6.18-6.10 (1H, m), 3.16-2.20 (5H, m), 2.13 (3H, d, J=4.8 Hz), 2.06-1.70 (3H, m), 1.23 (3H, dt, J=7.4, 4.4 Hz). MS (NH₃-CI): m/e calc'd for C₂₄H₂₃Cl₂N₄: 437.1300, found 437.1299; 439 (67), 437 (100).

Example 2223 spectral data: TLC R_(F) 0.36 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.33 (1H, s), 6.83 (1H, s), 4.78 (1H, pentet, J=8.5 Hz), 3.94 (3H, s), 3.90 (3H, s), 2.98 (2H, q, J=7.6 Hz), 2.58-2.48 (2H, m), 2.42 (3H, s), 2.19-2.07 (2H, m), 1.84-1.56 (4H, m), 1.43 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₂₁H₂₇N₄O₂: 367.2134, found 367.2120; 369 (3), 368 (24), 367 (100).

Example 2227 spectral data: TLC R_(F) 0.45 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.90 (1H, s), 7.37 (1H, s), 6.83 (1H, s), 4.85 (1H, q, J=8.4 Hz), 3.94 (3H, s), 3.91 (3H, s), 3.19-3.11 (1H, m), 2.96 (2H, dq, J=7.9, 1.5 Hz), 2.41 (3H, s), 2.24-2.16 (2H, m), 2.04-1.94 (2H, m), 1.71-1.62 (2H, m), 1.44 (3H, t, J=7.4 Hz), 0.69 (3H, d, J=6.9 Hz). MS (NH₃-CI): m/e calc'd for C₂₂H₂₉N₄O₂: 381.2290, found 381.2294; 383 (4), 382 (25), 381 (100).

The methods discussed below in the preparation of 3-benzyl-5-methyl-7-(2,4,6-trimethylphenyl)-imidazo[4,5-b]pyridine (Example 3001, Table 3) may be used to prepare all of the examples of Structure A contained in Table 3, with minor procedural modifications where necessary and use of reagents of the appropriate structure.

The methods of Schemes 13 and 14 may be used to prepare many of the examples of Structure B and Structure C contained in Table 3, with minor procedural modifications where necessary and use of reagents of the appropriate structure.

EXAMPLE 3001 Preparation of 3-benzyl-5-methyl-7-(2,4,6-trimethylphenyl)imidazo[4, 5-b]pyridine

Part A. A solution of 2,4,6-trimethylbenzeneboronic acid in benzene (0.5 M) is treated with excess n-butanol, and the solution is heated to reflux under a Dean-Stark still head to azeotropically remove water. Solvent is removed by evaporation, and the resulting dibutyl 2,4,6-trimethylbenzeneboronate is used directly in Part B.

Part B. The method of Snieckus et al. (Fu, J. M.; Zhao, B. P.; Sharp, M. J.; Snieckus, V. Can. J. Chem. 1994, 72, 227-236) may be employed here. Thus, a solution of 4-chloro-6-methyl-3-nitro-2-pyridone in dimethylformamide (0.1 M) is treated with the boronate from Part A (1.2 eq), tribasic potassium phosphate (2.4 eq), and [1,1′-bis (diphenylphosphino) -ferrocene]dichloropalladium (0.1 eq). The mixture is stirred at ambient temperature for 30 hrs., then poured into 4 volumes ethyl acetate. This is washed with 3 equal volumes of water, then brine. The extract is dried over Na₂SO₄, filtered and evaporated. Chromatographic separation affords pure 6-methyl-3-nitro-4-(2,4, 6-trimethylphenyl)-2-pyridone.

Part C. The pyridone from Part B is suspended in 6 eq phosphorus oxychloride, and stirred with mild heating until the compound dissolves. The mixture is cooled, and poured over ice. After melting, the mixture is extracted twice with dichloromethane, and the extracts are combined, dried over Na₂SO₄, filtered and evaporated. The product, 2-chloro-6-methyl-3-nitro-4-(2,4,6-trimethylphenyl)pyridine, is purified by either chromatography or recrystallization.

Part D. The chloride from Part C is dissolved in ethanol, and treated with benzylamine (1.2 eq.). The mixture is heated to reflux until the starting material is consumed as determined by thin-layer chromatography. The mixture is evaporated, and the residual material is partitioned between water and ethyl acetate. The organic layer is separated, washed with brine, dried over Na₂SO₄, filtered and evaporated. The product, 2-benzylamino-6-methyl-3-nitro-4-(2,4,6-trimethylphenyl)pyridine, is purified by either chromatography or recrystallization.

Part E. The nitro compound from Part D is dissolved in 1:1 aqueous dioxane, and treated with conc. aq. ammonium hydroxide solution. To this is added solid sodium dithionite in several portions over 2 h. The mixture is allowed to stir for an additional 4 h, then partitioned between water and ethyl acetate. The organic layer is separated, washed with brine, dried over Na₂SO₄, filtered and evaporated. The product, 3-amino-2-benzylamino-6-methyl-4-(2,4,6-trimethylphenyl)pyridine, is purified by either chromatography or recrystallization.

Part F. A suspension of the diamine from Part E above in triethyl orthopropionate is treated with conc. HCl, and heated to reflux for 1 h, then cooled and the excess orthoester removed by vacuum distillation. The pot residue contains sufficiently pure N-[2-benzylamino-4-(2,4,6-trimethylphenyl)-6-methylpyridin-3-yl]propionamide O-ethyl imidate.

Part G. A solution of the compound from Part F in phenyl ether is treated with a catalytic amount of p-toluenesulfonic acid and heated to 170° C. for 6 h, then cooled. The residual liquid is separated by column chromatography (hexane, then ethyl acetate) to afford the title product.

TABLE 3 (A)

(B)

(C)

mp, Ex. No. X R⁴ R⁵ R¹¹ R⁶ R¹ ° C.^(a) 3001 CH₂ Cl Cl H H C(═O)OC₂H₅ — 3002 CH₂ Cl Cl H H C(═O)OC₃H₇ 90-91 3003 CH₂ Cl Cl H H C(═O)OC₄H₉ 57-59 3004 CH₂ Cl Cl H H C(═O)OCH(CH₃)₂ 80-81 3005 CH₂ Cl Cl H H C(═O)OCH₂CH(CH₃)₂ 60-62 3006 CH₂ Cl Cl H H C(═O)N(CH₃)₂ — 3007 CH₂ Cl Cl H H C(═O)N(C₂H₅)₂ 120-123 3008 CH₂ Cl Cl H H C(═O)N[CH(CH₃)₂]₂ 147-149 3009 CH₂ Cl Cl H H C(═O)(1-morpholinyl) 158-159 3010 CH₂ Cl Cl H H SO₂C₆H₅ 132-133 3011 CH₂ Cl Cl H H SO₂(4-CH₃—C₆H₄) 154-155 3012 CH₂ Cl Cl H H SO₂(4-OCH₃—C₆H₄) 156-158 3013 CH₂ Cl Cl H H SO₂-(2-thienyl) 176-178 3014 CH₂ Cl Cl H H SO₂CH₂C₆H₅ 127-129 3015 CH₂ Cl Cl H H SO₂C₃H₇ 100-101 3016 CH₂ Cl Cl H H SO₂C₄H₉ 79-80 3017 CH₂ Cl Cl H H C(═O)-(2-Cl—C₆H₄) 110-113 3018 CH₂ Cl CF₃ H H C(═O)OC₂H₅ — 3019 CH₂ Cl CF₃ H H C(═O)OC₃H₇ — 3020 CH₂ Cl CF₃ H H C(═O)OC₄H₉ — 3021 CH₂ Cl CF₃ H H C(═O)OCH(CH₃)₂ — 3022 CH₂ Cl CF₃ H H C(═O)OCH₂CH(CH₃)₂ — 3023 CH₂ Cl CF₃ H H C(═O)N(CH₃)₂ — 3024 CH₂ Cl CF₃ H H C(═O)N(C₂H₅)₂ — 3025 CH₂ Cl CF₃ H H C(═O)N[CH(CH₃)₂]₂ 3026 CH₂ Cl CF₃ H H C(═O)(1-morpholinyl) — 3027 CH₂ Cl CF₃ H H SO₂C₆H₅ — 3028 CH₂ Cl CF₃ H H SO₂(4-CH₃—C₆H₄) — 3029 CH₂ Cl CF₃ H H SO₂2(4-OCH₃—C₆H₄) — 3030 CH₂ Cl CF₃ H H SO₂-(2-thienyl) — 3031 CH₂ Cl CF₃ H H SO₂CH₂C₆H₅ — 3032 CH₂ Cl CF₃ H H SO₂C₃H₇ — 3033 CH₂ Cl CF₃ H H SO₂C₄H₉ 3034 CH₂ Cl CF₃ H H C(═O)-(2-Cl—C₆H₄) — 3035 CH₂ Cl OCH₃ H H C(═O)OC₂H₅ — 3036 CH Cl OCH₃ H H C(═O)OC₃H₇ — 3037 CH₂ Cl OCH₃ H H C(═O)OC₄H₉ — 3038 CH₂ Cl OCH₃ H H C(═O)OCH(CH₃)₂ — 3039 CH₂ Cl OCH₃ H H C(═O)OCH₂CH(CH₃)₂ — 3040 CH₂ Cl OCH₃ H H C(═O)N(CH₃)₂ — 3041 CH₂ Cl OCH₃ H H C(═O)N(C₂H₅)₂ — 3042 CH₂ Cl OCH₃ H H C(═O)N[CH(CH₃)₂]₂ — 3043 CH₂ Cl OCH₃ H H C(═O)(1-morpholinyl) — 3044 CH₂ Cl OCH₃ H H SO₂C₆H₅ — 3045 CH₂ Cl OCH₃ H H SO₂(4-CH₃—C₆H₄) — 3046 CH₂ Cl OCH₃ H H SO₂(4-OCH₃—C₆H₄) — 3047 CH₂ Cl OCH₃ H H SO₂(2-thienyl) — 3048 CH₂ Cl OCH₃ H H SO₂CH₂C₆H₅ — 3049 CH₂ Cl OCH₃ H H SO₂C₃H₇ — 3050 CH₂ Cl OCH₃ H H SO₂C₄H₉ — 3051 CH₂ Cl OCH₃ H H C(═O)-(2-Cl—C₆H₄) — 3052 CH₂ Cl OCF₃ H H C(═O)OC₂H₅ — 3053 CH₂ Cl OCF₃ H H C(═O)OC₃H₇ — 3054 CH₂ Cl OCF₃ H H C(═O)OC₄H₉ — 3055 CH₂ Cl OCF₃ H H C(═O)OCH(CH₃)₂ — 3056 CH₂ Cl OCF₃ H H C(═O)OCH₂CH(CH₃)₂ — 3057 CH₂ Cl OCF₃ H H C(═O)N(CH₃)₂ — 3058 CH₂ Cl OCF₃ H H C(═O)N(C₂H₅)₂ — 3059 CH₂ Cl OCF₃ H H C(═O)N[CH(CH₃)₂]₂ — 3060 CH₂ Cl OCF₃ H H C(═O)(1-morpholinyl) — 3061 CH₂ Cl OCF₃ H H SO₂C₆H₅ — 3062 CH₂ Cl OCF₃ H H SO₂(4-CH₃—C₆H₄) — 3063 CH₂ Cl OCF₃ H H SO₂(4-OCH₃—C₆H₄) — 3064 CH₂ Cl OCF₃ H H SO₂-(2-thienyl) — 3065 CH₂ Cl OCF₃ H H SO₂CH₂C₆H₅ — 3066 CH₂ Cl OCF₃ H H SO₂C₃H₇ — 3067 CH₂ Cl OCF₃ H H SO₂C₄H₉ — 3068 CH₂ Cl OCF₃ H H C(═O)-(2-Cl—C₆H₄) — 3069 CH₂ Cl CH₃ H H C(═O)OC₂H₅ — 3070 CH₂ Cl CH₃ H H C(═O)OC₃H₇ — 3071 CH₂ Cl CH₃ H H C(═O)OC₄H₉ — 3072 CH₂ Cl CH₃ H H C(═O)OCH(CH₃)₂ — 3073 CH₂ Cl CH₃ H H C(═O)OCH₂CH(CH₃)₂ — 3674 CH₂ Cl CH₃ H H C(═O)N(CH₃)₂ — 3075 CH₂ Cl CH₃ H H C(═O)N(C₂H₅)₂ — 3076 CH₂ Cl CH₃ H H C(═O)N[CH(CH₃)₂]₂ — 3077 CH₂ Cl CH₃ H H C(═O)(1-morpholinyl) — 3078 CH₂ Cl CH₃ H H SO₂C₆H₅ — 3079 CH₂ Cl CH₃ H H SO₂(4-CH₃—C₆H₄) — 3080 CH₂ Cl CH₃ H H SO₂(4-OCH₃—C₆H₄) — 3081 CH₂ Cl CH₃ H H SO₂(2-thienyl) — 3082 CH₂ Cl CH₃ H H SO₂CH₂C₆H₅ — 3083 CH₂ Cl CH₃ H H SO₂C₃H₇ 3084 CH₂ CH₃ CH₃ H H SO₂C₄H₉ — 3085 CH₂ Cl CH₃ H H C(═O)-(2-Cl—C₆H₄) — 3086 CH₂ CF₃ Cl H H C(═O)OC₂H₅ — 3087 CH₂ CF₃ Cl H H C(═O)OC₃H₇ — 3088 CH₂ CF₃ Cl H H C(═O)OC₄H₉ — 3089 CH₂ CF₃ Cl H H C(═O)OCH(CH₃)₂ — 3090 CH₂ CF₃ Cl H H C(═O)OCH₂CH(CH₃)₂ — 3091 CH₂ CF₃ Cl H H C(═O)N(CH₃)₂ — 3092 CH₂ CF₃ Cl H H C(═O)N(C₂H₅)₂ — 3093 CH₂ CF₃ Cl H H C(═O)N[CH(CH₃)₂]₂ — 3094 CH₂ CF₃ Cl H H C(═O) (1-morpholinyl) — 3095 CH₂ CF₃ Cl H H SO₂C₆H₅ — 3096 CH₂ CF₃ Cl H H SO₂(4-CH₃—C₆H₄) — 3097 CH₂ CF₃ Cl H H SO₂(4-OCH₃—C₆H₄) — 3098 CH₂ CF₃ Cl H H SO₂-(2-thienyl) — 3099 CH₂ CF₃ Cl H H SO₂CH₂C₆H₅ — 3100 CH₂ CF₃ Cl H H SO₂C₃H₇ — 3101 CH₂ CF₃ Cl H H SO₂C₄H₉ — 3102 CH₂ CF₃ Cl H H C(═O)-(2-Cl—C₆H₄) — 3103 CH₂ CF₃ OCH₃ H H C(═O)OC₂H₅ — 3104 CH₂ CF₃ OCH₃ H H C(═O)OC₃H₇ — 3105 CH₂ CF₃ OCH₃ H H C(═O)OC₄H₉ — 3106 CH₂ CF₃ OCH₃ H H C(═O)OCH(CH₃)₂ — 3107 CH₂ CF₃ OCH₃ H H C(═O)OCH₂CH(CH₃)₂ — 3108 CH₂ CF₃ OCH₃ H H C(═O)N(CH₃)₂ — 3109 CH₂ CF₃ OCH₃ H H C(═O)N(C₂H₅)₂ — 3110 CH₂ CF₃ OCH₃ H H C(═O)N[CH(CH₃)₂]₂ — 3111 CH₂ CF₃ OCH₃ H H C(═O)(1-morpholinyl) — 3112 CH₂ CF₃ OCH₃ H H SO₂C₆H₅ — 3113 CH₂ CF₃ OCH₃ H H SO₂(4-CH₃—C₆H₄) — 3114 CH₂ CF₃ OCH₃ H H SO₂(4-OCH₃—C₆H₄) — 3115 CH₂ CF₃ OCH₃ H H SO₂-(2-thienyl) — 3116 CH₂ CF₃ OCH₃ H H SO₂CH₂C₆H₅ — 3117 CH₂ CF₃ OCH₃ H H SO₂C₃H₇ — 3118 CH₂ CF₃ OCH₃ H H SO₂C₄H₉ — 3119 CH₂ CF₃ OCH₃ H H C(═O)-(2-Cl—C₆H₄) — 3120 CH₂ CF₃ F H H C(═O)OC₂H₅ — 3121 CH₂ CF₃ F H H C(═O)OC₃H₇ — 3122 CH₂ CF₃ F H H C(═O)OC₄H₉ — 3123 CH₂ CF₃ F H H C(═O)OCH(CH₃)₂ — 3124 CH₂ CF₃ F H H C(═O)OCH₂CH(CH₃)₂ — 3125 CH₂ CF₃ F H H C(═O)N(CH₃)₂ — 3126 CH₂ CF₃ F H H C(═O)N(C₂H₅)₂ — 3127 CH₂ CF₃ F H H C(═O)N[CH(CH₃)₂]₂ — 3128 CH₂ CF₃ F H H C(═O)(1-morpholinyl) — 3129 CH₂ CF₃ F H H SO₂C₆H₅ — 3130 CH₂ CF₃ F H H SO₂(4-CH₃—C₆H₄) — 3131 CH₂ CF₃ F H H SO₂(4-OCH₃—C₆H₄) — 3132 CH₂ CF₃ F H H SO₂(2-thienyl) — 3133 CH₂ CF₃ F H H SO₂CH₂C₆H₅ — 3134 CH₂ CF₃ F H H SO₂C₃H₇ — 3135 CH₂ CF₃ F H H SO₂C₄H₉ — 3136 CH₂ CF₃ F H H C(═O)-(2-Cl—C₆H₄) — 3137 CH₂ CH₃ OCH₃ CH₃ H C(═O)OC₂H₅ — 3138 CH₂ CH₃ OCH₃ CH₃ H C(═O)OC₃H₇ — 3139 CH₂ CH₃ OCH₃ CH₃ H C(═O)OC₄H₉ — 3140 CH₂ CH₃ OCH₃ CH₃ H C(═O)OCH(CH₃)₂ — 3141 CH₂ CH₃ OCH₃ CH₃ H C(═O)OCH₂CH(CH₃)₂ — 3142 CH₂ CH₃ OCH₃ CH₃ H C(═O)N(CH₃)₂ — 3143 CH₂ CH₃ OCH₃ CH₃ H C(═O) N(C₂H₅)₂ — 3144 CH₂ CH₃ OCH₃ CH₃ H C(═O)N[CH(CH₃)₂]₂ — 3145 CH₂ CH₃ OCH₃ CH₃ H C(═O)(1-morpholinyl) — 3146 CH₂ CH₃ OCH₃ CH₃ H SO₂C₆H₅ — 3147 CH₂ CH₃ OCH₃ CH₃ H SO₂(4-CH₃—C₆H₄) — 3148 CH₂ CH₃ OCH₃ CH₃ H SO₂(4-OCH₃—C₆H₄) — 3149 CH₂ CH₃ OCH₃ CH₃ H SO₂-(2-thienyl) — 3150 CH₂ CH₃ OCH₃ CH₃ H SO₂CH₂C₆H₅ — 3151 CH₂ CH₃ OCH₃ CH₃ H SO₂C₃H₇ — 3152 CH₂ CH₃ OCH₃ CH₃ H SO₂C₄H₉ — 3153 CH₂ CH₃ OCH₃ CH₃ H C(═O)-(2-Cl—C₆H₄) — 3152 CH₂ CH₃ OCH₃ CH₃ H C(═O)OC₂H₅ — 3155 CH₂ CH₃ OCH₃ Cl H C(═O)OC₃H₇ — 3156 CH₂ CH₃ OCH₃ Cl H C(═O)OC₄H₉ — 3157 CH₂ CH₃ OCH₃ Cl H C(═O)OCH(CH₃)₂ — 3158 CH₂ CH₃ OCH₃ Cl H C(═O)OCH₂CH(CH₃)₂ — 3159 CH₂ CH₃ OCH₃ Cl H C(═O)N(CH₃)₂ — 3160 CH₂ CH₃ OCH₃ Cl H C(═O)N(C₂H₅)₂ — 3161 CH₂ CH₃ OCH₃ Cl H C(═O)N[CH(CH₃)₂]₂ — 3162 CH₂ CH₃ OCH₃ Cl H C(═O)(1-morpholinyl) — 3163 CH₂ CH₃ OCH₃ Cl H SO₂C₆H₅ — 3164 CH₂ CH₃ OCH₃ Cl H SO₂(4-CH₃—C₆H₄) — 3165 CH₂ CH₃ OCH₃ Cl H SO₂(4-OCH₃—C₆H₄) — 3166 CH₂ CH₃ OCH₃ Cl H SO₂-(2-thienyl) — 3167 CH₂ CH₃ OCH₃ Cl H SO₂CH₂C₆H₅ — 3168 CH₂ CH₃ OCH₃ Cl H SO₂C₃H₇ — 3169 CH₂ CH₃ OCH₃ Cl H SO₂C₄H₉ — 3170 CH₂ CH₃ OCH₃ Cl H C(═O)-(2-Cl—C₆H₄) — 3171 CH₂ CH₃ OCH₃ F H C(═O)OC₂H₅ — 3172 CH₂ CH₃ OCH₃ F H C(═O)OC₃H₇ — 3173 CH₂ CH₃ OCH₃ F H C(═0)OC₄H₉ — 3174 CH₂ CH₃ OCH₃ F H C(═O)OCH(CH₃)₂ — 3175 CH₂ CH₃ OCH₃ F H C(═O)OCH₂CH(CH₃)₂ — 3176 CH₂ CH₃ OCH₃ F H C(═O)N(CH₃)₂ — 3177 CH₂ CH₃ OCH₃ F H C(═O)N(C₂H₅)₂ — 3178 CH₂ CH₃ OCH₃ F H C(═O)N[CH(CH₃)₂]₂ — 3179 CH₂ CH₃ OCH₃ F H C(═O)(1-morpholinyl) — 3180 CH₂ CH₃ OCH₃ F H SO₂C₆H₅ — 3181 CH₂ CH₃ OCH₃ F H SO₂(4-CH₃—C₆H₄) — 3182 CH₂ CH₃ OCH₃ F H SO₂(4-OCH₃—C₆H₄) — 3183 CH₂ CH₃ OCH₃ F H SO₂-(2-thienyl) — 3184 CH₂ CH₃ OCH₃ F H SO₂CH₂C₆H₅ — 3185 CH₂ CH₃ OCH₃ F H SO₂C₃H₇ — 3186 CH₂ CH₃ OCH₃ F H SO₂C₄H₉ — 3187 CH₂ CH₃ OCH₃ F H C(═O)-(2-Cl—C₆H₄) — 3188 CH₂ CH₃ CH₃ H CH₃ C(═O)OC₂H₅ — 3189 CH₂ CH₃ CH₃ H CH₃ C(═O)OC₃H₇ — 3190 CH₂ CH₃ CH₃ H CH₃ C(═O)OC₄H₉ — 3191 CH₂ CH₃ CH₃ H CH₃ C(═O)OCH(CH₃)₂ — 3192 CH₂ CH₃ CH₃ H CH₃ C(═O)OCH₂CH(CH₃)₂ — 3193 CH₂ CH₃ CH₃ H CH₃ C(═O)N(CH₃)₂ — 3194 CH₂ CH₃ CH₃ H CH₃ C(═O)N(C₂H₅)₂ — 3195 CH₂ CH₃ CH₃ H CH₃ C(═O)N[CH(CH₃)₂]₂ — 3196 CH₂ CH₃ CH₃ H CH₃ C(═O)(1-morpholinyl) — 3197 CH₂ CH₃ CH₃ H CH₃ SO₂C₆H₅ — 3198 CH₂ CH₃ CH₃ H CH₃ SO₂(4-CH₃—C₆H₄) — 3199 CH₂ CH₃ CH₃ H CH₃ SO₂(4-OCH₃—C₆H₄) — 3200 CH₂ CH₃ CH₃ H CH₃ SO₂-(2-thienyl) — 3201 CH₂ CH₃ CH₃ H CH₃ SO₂CH₂C₆H₅ — 3202 CH₂ CH₃ CH₃ H CH₃ SO₂C₃H₇ — 3203 CH₂ CH₃ CH₃ H CH₃ SO₂C₄H₉ — 3204 CH₂ CH₃ CH₃ H CH₃ C(═O)-(2-Cl—C₆H₄) — 3205 CH₂ Cl Cl H CH₃ C(═O)OC₂H₅ — 3206 CH₂ Cl Cl H CH₃ C(═O)OC₃H₇ — 3207 CH₂ Cl Cl H CH₃ C(═O)OC₄H₉ — 3208 CH₂ Cl Cl H CH₃ C(═O)OCH(CH₃)₂ — 3209 CH₂ Cl Cl H CH₃ C(═O)OCH₂CH(CH₃)₂ — 3210 CH₂ Cl Cl H CH₃ C(═O)N(CH₃)₂ — 3211 CH₂ Cl Cl H CH₃ C(═O)N(C₂H₅)₂ — 3212 CH₂ Cl Cl H CH₃ C(═O)N[CH(CH₃)₂]₂ — 3213 CH₂ Cl Cl H CH₃ C(═O)(1-morpholinyl) — 3214 CH₂ Cl Cl H CH₃ SO₂C₆H₅ — 3215 CH₂ Cl Cl H CH₃ SO₂(4-CH₃—C₆H₄) — 3216 CH₂ Cl Cl H CH₃ SO₂(4-OCH₃—C₆H₄) — 3217 CH₂ Cl Cl H CH₃ SO₂(2-thienyl) — 3218 CH₂ Cl Cl H CH₃ SO₂CH₂C₆H₅ — 3219 CH₂ Cl Cl H CH₃ SO₂C₃H₇ — 3220 CH₂ Cl Cl H CH₃ SO₂C₄H₉ — 3221 CH₂ Cl Cl H CH₃ C(═O)-(2-Cl—C₆H₄) — 3222 CH₂ CH₃ OCH₃ OCH₃ H C(═O)OC₂H₅ — 3223 CH₂ CH₃ OCH₃ OCH₃ H C(═O)OC₃H₇ — 3224 CH₂ CH₃ OCH₃ OCH₃ H C(═O)OC₄H₉ — 3225 CH₂ CH₃ OCH₃ OCH₃ H C(═O)OCH(CH₃)₂ — 3226 CH₂ CH₃ OCH₃ OCH₃ H C(═O)OCH₂CH(CH₃)₂ — 3227 CH₂ CH₃ OCH₃ OCH₃ H C(═O)N(CH₃)₂ — 3228 CH₂ CH₃ OCH₃ OCH₃ H C(═O)N(C₂H₅)₂ — 3229 CH₂ CH₃ OCH₃ OCH₃ H C(═O)N[CH(CH₃)₂]₂ — 3230 CH₂ CH₃ OCH₃ OCH₃ H C(═O)(1-morpholinyl) — 3231 CH₂ CH₃ OCH₃ OCH₃ H SO₂C₆H₅ — 3232 CH₂ CH₃ OCH₃ OCH₃ H SO₂(4-CH₃—C₆H₄) — 3233 CH₂ CH₃ OCH₃ OCH₃ H SO₂(4-OCH₃—C₆H₄) — 3234 CH₂ CH₃ OCH₃ OCH₃ H SO₂-(2-thienyl) — 3235 CH₂ CH₃ OCH₃ OCH₃ H SO₂CH₂C₆H₅ — 3236 CH₂ CH₃ OCH₃ OCH₃ H SO₂C₃H₇ — 3237 CH₂ CH₃ OCH₃ OCH₃ H SO₂C₄H₉ — 3238 CH₂ CH₃ OCH₃ OCH₃ H C(═O)-(2-Cl—C₆H₄) — 3239 O Cl Cl H H SO₂C₃H₇ — 3240 O Cl CF₃ H H SO₂C₃H₇ — 3241 O Cl OCH₃ H H SO₂C₃H₇ — 3242 O Cl OCF₃ H H SO₂C₃H₇ — 3243 O Cl CH₃ H H SO₂C₃H₇ — 3244 O CF₃ Cl H H SO₂C₃H₇ — 3245 O CF₃ OCH₃ H H SO₂C₃H₇ — 3246 O CH₃ OCH₃ CH₃ H SO₂C₃H₇ — 3247 O CH₃ OCH₃ Cl H SO₂C₃H₇ — 3248 O CH₃ OCH₃ F H SO₂C₃H₇ — 3249 O CH₃ CH₃ H CH₃ SO₂C₃H₇ — 3250 O Cl Cl H CH₃ SO₂C₃H₇ — 3251 CH₂ Cl Cl H H C(═O)-(3-Cl—C₆H₄) 115—118

The methods used in the preparation of the compounds of Structure A of Table 1 may be used for the compounds of Structure A of Table 4. For example, replacing variously-substituted pyridine- and pyrimidineboronic acids for benzeneboronic acids in the palladium-catalyzed aryl cross-coupling method (see Examples 35 or 831) will afford the desired 6-pyridyl- or 6-pyrimidylpurine compounds.

The methods of Schemes 13 and 14 may be used to prepare many of the examples of Structure B and Structure C contained in Table 4, with minor procedural modifications where necessary and use of reagents of the appropriate structure.

TABLE 4 (A)

(B)

(C)

m.p., Ex. No. X R⁴ Z R⁵ Y R⁶ R^(1a) R^(1b) ° C.^(a) 4001 CH₂ CH₃ CH N(CH₃)₂ N H c-C₃H₅ c-C₃H₅ — 4002 CH₂ CH₃ CH N(CH₃)₂ N H CH₃ c-C₃H₅ — 4003 CH₂ CH₃ CH N(CH₃)₂ N H C₂H₅ c-C₃H₅ — 4004 CH₂ CH₃ CH N(CH₃)₂ N H C₃H₇ c-C₃H₅ — 4005 CH₂ CH₃ CH N(CH₃)₂ N H C₄H₉ c-C₃H₅ — 4006 CH₂ CH₃ CH N(CH₃)₂ N H CH₃ C₃H₇ — 4007 CH₂ CH₃ CH N(CH₃)₂ N H C₂H₅ C₃H₇ — 4008 CH₂ CH₃ CH N(CH₃)₂ N H C₃H₇ C₃H₇ — 4009 CH₂ CH₃ CH N(CH₃)₂ N H C₂H₅ C₄H₉ — 4010 CH₂ CH₃ CH N(CH₃)₂ N H H 4-CH₃O—C₆H₄ — 4011 O CH₃ CH N(CH₃)₂ N H c-C₃H₅ c-C₃H₅ — 4012 O CH₃ CH N(CH₃)₂ N H CH₃ c-C₃H₅ — 4013 O CH₃ CH N(CH₃)₂ N H C₂H₅ c-C₃H₅ — 4014 O CH₃ CH N(CH₃)₂ N H C₃H₇ c-C₃H₅ — 4015 O CH₃ CH N(CH₃)₂ N H C₄H₉ c-C₃H₅ — 4016 O CH₃ CH N(CH₃)₂ N H CH₃ C₃H₇ — 4017 O CH₃ CH N(CH₃)₂ N H C₂H₅ C₃H₇ — 4018 O CH₃ CH N(CH₃)₂ N H C₃H₇ C₃H₇ — 4019 O CH₃ CH N(CH₃)₂ N H C₂H₅ C₄H₉ — 4020 O CH₃ CH N(CH₃)₂ N H H 4-CH₃O—C₆H₄ — 4021 CH₂ CH₃ CH CH₃ N CH₃ c-C₃H₅ c-C₃H₅ — 4022 CH₂ CH₃ CH CH₃ N CH₃ CH₃ c-C₃H₅ — 4023 CH₂ CH₃ CH CH₃ N CH₃ C₂H₅ c-C₃H₅ — 4024 CH₂ CH₃ CH CH₃ N CH₃ C₃H₇ c-C₃H₅ — 4025 CH₂ CH₃ CH CH₃ N CH₃ C₄H₉ c-C₃H₅ — 4026 CH₂ CH₃ CH CH₃ N CH₃ CH₃ C₃H₇ — 4027 CH₂ CH₃ CH CH₃ N CH₃ C₂H₅ C₃H₇ — 4028 CH₂ CH₃ CH CH₃ N CH₃ C₃H₇ C₃H₇ — 4029 CH₂ CH₃ CH CH₃ N CH₃ C₂H₅ C₄H₉ — 4030 CH₂ CH₃ CH CH₃ N CH₃ H 4-CH₃O—C₆H₄ — 4031 O CH₃ CH CH₃ N CH₃ c-C₃H₅ c-C₃H₅ — 4032 O CH₃ CH CH₃ N CH₃ CH₃ c-C₃H₅ — 4033 O CH₃ CH CH₃ N CH₃ C₂H₅ c-C₃H₅ — 4034 O CH₃ CH CH₃ N CH₃ C₃H₇ c-C₃H₅ — 4035 O CH₃ CH CH₃ N CH₃ C₄H₉ c-C₃H₅ — 4036 O CH₃ CH CH₃ N CH₃ CH₃ C₃H₇ — 4037 O CH₃ CH CH₃ N CH₃ C₂H₅ C₃H₇ — 4038 O CH₃ CH CH₃ N CH₃ C₃H₇ C₃H₇ — 4039 O CH₃ CH CH₃ N CH₃ C₂H₅ C₄H₉ — 4040 O CH₃ CH CH₃ N CH₃ H 4-CH₃O—C₆H₄ — 4041 CH₂ CH₃ CH SCH₃ N H c-C₃H₅ c-C₃H₅ — 4042 CH₂ CH₃ CH SCH₃ N H CH₃ c-C₃H₅ — 4043 CH₂ CH₃ CH SCH₃ N H C₂H₅ c-C₃H₅ — 4044 CH₂ CH₃ CH SCH₃ N H C₃H₇ c-C₃H₅ — 4045 CH₂ CH₃ CH SCH₃ N H C₄H₉ c-C₃H₅ — 4046 CH₂ CH₃ CH SCH₃ N H CH₃ C₃H₇ — 4047 CH₂ CH₃ CH SCH₃ N H C₂H₅ C₃H₇ — 4048 CH₂ CH₃ CH SCH₃ N H C₃H₇ C₃H₇ — 4049 CH₂ CH₃ CH SCH₃ N H C₂H₅ C₄H₉ — 4050 CH₂ CH₃ CH SCH₃ N H H 4-CH₃O—C₆H₄ — 4051 O CH₃ CH3 SCH₃ N H c-C₃H₅ c-C₃H₅ — 4052 O CH₃ CH3 SCH₃ N H CH₃ c-C₃H₅ — 4053 O CH₃ CH3 SCH₃ N H C₂H₅ c-C₃H₅ — 4054 O CH₃ CH3 SCH₃ N H C₃H₇ c-C₃H₅ — 4055 O CH₃ CH3 SCH₃ N H C₄H₉ c-C₃H₅ — 4056 O CH₃ CH3 SCH₃ N H CH₃ C₃H₇ — 4057 O CH₃ CH3 SCH₃ N H C₂H₅ C₃H₇ — 4058 O CH₃ CH3 SCH₃ N H C₃H₇ C₃H₇ — 4059 O CH₃ CH3 SCH₃ N H C₂H₅ C₄H₉ — 4060 O CH₃ CH3 SCH₃ N H H 4-CH₃O—C₆H₄ — 4061 CH₂ SCH₃ N CH₃ N SCH₃ c-C₃H₅ c-C₃H₅ — 4062 CH₂ SCH₃ N CH₃ N SCH₃ CH₃ c-C₃H₅ — 4063 CH₂ SCH₃ N CH₃ N SCH₃ C₂H₅ c-C₃H₅ — 4064 CH₂ SCH₃ N CH₃ N SCH₃ C₃H₇ c-C₃H₅ — 4065 CH₂ SCH₃ N CH₃ N SCH₃ C₄H₉ c-C₃H₅ — 4066 CH₂ SCH₃ N CH₃ N SCH₃ CH₃ C₃H₇ — 4067 CH₂ SCH₃ N CH₃ N SCH₃ C₂H₅ C₃H₇ — 4068 CH₂ SCH₃ N CH₃ N SCH₃ C₃H₇ C₃H₇ — 4069 CH₂ SCH₃ N CH₃ N SCH₃ C₂H₅ C₄H₉ — 4070 CH₂ SCH₃ N CH₃ N SCH₃ H 4-CH₃O—C₆H₄ — 4071 O SCH₃ N CH₃ N SCH₃ c-C₃H₅ c-C₃H₅ — 4072 O SCH₃ N CH₃ N SCH₃ CH₃ c-C₃H₅ — 4073 O SCH₃ N CH₃ N SCH₃ C₂H₅ c-C₃H₅ — 4074 O SCH₃ N CH₃ N SCH₃ C₃H₇ c-C₃H₅ — 4075 O SCH₃ N CH₃ N SCH₃ C₄H₉ c-C₃H₅ — 4076 O SCH₃ N CH₃ N SCH₃ CH₃ C₃H₇ — 4077 O SCH₃ N CH₃ N SCH₃ C₂H₅ C₃H₇ — 4078 O SCH₃ N CH₃ N SCH₃ C₃H₇ C₃H₇ — 4079 O SCH₃ N CH₃ N SCH₃ C₂H₅ C₄H₉ — 4080 O SCH₃ N CH₃ N SCH₃ H 4-CH₃O—C₆H₄ — 4081 CH₂ CH₃ N CH₃ N CH₃ c-C₃H₅ c-C₃H₅ — 4082 CH₂ CH₃ N CH₃ N CH₃ CH₃ c-C₃H₅ — 4083 CH₂ CH₃ N CH₃ N CH₃ C₂H₅ c-C₃H₅ — 4084 CH₂ CH₃ N CH₃ N CH₃ C₃H₇ c-C₃H₅ — 4085 CH₂ CH₃ N CH₃ N CH₃ C₄H₉ c-C₃H₅ — 4086 CH₂ CH₃ N CH₃ N CH₃ CH₃ C₃H₇ — 4087 CH₂ CH₃ N CH₃ N CH₃ C₂H₅ C₃H₇ — 4088 CH₂ CH₃ N CH₃ N CH₃ C₃H₇ C₃H₇ — 4089 CH₂ CH₃ N CH₃ N CH₃ C₂H₅ C₄H₉ — 4090 CH₂ CH₃ N CH₃ N CH₃ H 4-CH₃O—C₆H₄ — 4091 O CH₃ N CH₃ N CH₃ c-C₃H₅ c-C₃H₅ — 4092 O CH₃ N CH₃ N CH₃ CH₃ c-C₃H₅ — 4093 O CH₃ N CH₃ N CH₃ C₂H₅ c-C₃H₅ — 4094 O CH₃ N CH₃ N CH₃ C₃H₇ c-C₃H₅ — 4095 O CH₃ N CH₃ N CH₃ C₄H₉ c-C₃H₅ — 4096 O CH₃ N CH₃ N CH₃ CH₃ C₃H₇ — 4097 O CH₃ N CH₃ N CH₃ C₂H₅ C₃H₇ — 4098 O CH₃ N CH₃ N CH₃ C₃H₇ C₃H₇ — 4099 O CH₃ N CH₃ N CH₃ C₂H₅ C₄H₉ — 4100 O CH₃ N CH₃ N CH₃ H 4-CH₃O—C₆H₄ — 4101 CH₂ CH₃ CH CH₃ N H c-C₃H₅ c-C₃H₅ — 4102 CH₂ CH₃ CH CH₃ N H CH₃ c-C₃H₅ — 4103 CH₂ CH₃ CH CH₃ N H C₂H₅ c-C₃H₅ — 4104 CH₂ CH₃ CH CH₃ N H C₃H₇ c-C₃H₅ — 4105 CH₂ CH₃ CH CH₃ N H C₄H₉ c-C₃H₅ — 4106 CH₂ CH₃ CH CH₃ N H CH₃ C₃H₇ — 4107 CH₂ CH₃ CH CH₃ N H C₂H₅ C₃H₇ — 4108 CH₂ CH₃ CH CH₃ N H C₃H₇ C₃H₇ — 4109 CH₂ CH₃ CH CH₃ N H C₂H₅ C₄H₉ — 4110 CH₂ CH₃ CH CH₃ N H H 4-CH₃O—C₆H₄ — 4111 O CH₃ CH CH₃ N H c-C₃H₉ c-C₃H₅ — 4112 O CH₃ CH CH₃ N H CH₃ c-C₃H₅ — 4113 O CH₃ CH CH₃ N H C₂H₅ c-C₃H₅ — 4114 O CH₃ CH CH₃ N H C₃H₇ c-C₃H₅ — 4115 O CH₃ CH CH₃ N H C₄H₉ c-C₃H₅ — 4116 O CH₃ CH CH₃ N H CH₃ C₃H₇ — 4117 O CH₃ CH CH₃ N H C₂H₅ C₃H₇ — 4118 O CH₃ CH CH₃ N H C₃H₇ C₃H₇ — 4119 O CH₃ CH CH₃ N H C₂H₅ C₄H₉ — 4120 O CH₃ CH CH₃ N H H 4-CH₃O—C₆H₄ — 4121 CH₂ CH₃ N N(CH₃)₂ CH H c-C₃H₅ c-C₃H₅ — 4122 CH₂ CH₃ N N(CH₃)₂ CH H CH₃ c-C₃H₅ — 4123 CH₂ CH₃ N N(CH₃)₂ CH H C₂H₅ c-C₃H₅ — 4124 CH₂ CH₃ N N(CH₃)₂ CH H C₃H₇ c-C₃H₅ — 4125 CH₂ CH₃ N N(CH₃)₂ CH H C₄H₉ c-C₃H₅ — 4126 CH₂ CH₃ N N(CH₃)₂ CH H CH₃ C₃H₇ — 4127 CH₂ CH₃ N N(CH₃)₂ CH H C₂H₅ C₃H₇ — 4128 CH₂ CH₃ N N(CH₃)₂ CH H C₃H₇ C₃H₇ — 4129 CH₂ CH₃ N N(CH₃)₂ CH H C₂H₅ C₄H₉ — 4130 CH₂ CH₃ N N(CH₃)₂ CH H H 4-CH₃O—C₆H₄ — 4131 O CH₃ N N(CH₃)₂ CH H c-C₃H₅ c-C₃H₅ — 4132 O CH₃ N N(CH₃)₂ CH H CH₃ c-C₃H₅ — 4133 O CH₃ N N(CH₃)₂ CH H C₂H₅ c-C₃H₅ — 4134 O CH₃ N N(CH₃)₂ CH H C₃H₇ c-C₃H₅ — 4135 O CH₃ N N(CH₃)₂ CH H C₄H₉ c-C₃H₅ — 4136 O CH₃ N N(CH₃)₂ CH H CH₃ C₃H₇ — 4137 O CH₃ N N(CH₃)₂ CH H C₂H₅ C₃H₇ — 4138 O CH₃ N N(CH₃)₂ CH H C₃H₇ C₃H₇ — 4139 O CH₃ N N(CH₃)₂ CH H C₂H₅ C₄H₉ — 4140 O CH₃ N N(CH₃)₂ CH H H 4-CH₃O—C₆H₄ — 4141 CH₂ CH₃ N CH₃ CH H c-C₃H₅ c-C₃H₅ — 4142 CH₂ CH₃ N CH₃ CH H CH₃ c-C₃H₅ — 4143 CH₂ CH₃ N CH₃ CH H C₂H₅ c-C₃H₅ — 4144 CH₂ CH₃ N CH₃ CH H C₃H₇ c-C₃H₅ — 4145 CH₂ CH₃ N CH₃ CH H C₄H₉ c-C₃H₅ — 4146 CH₂ CH₃ N CH₃ CH H CH₃ C₃H₇ — 4147 CH₂ CH₃ N CH₃ CH H C₂H₅ C₃H₇ — 4148 CH₂ CH₃ N CH₃ CH H C₃H₇ C₃H₇ — 4149 CH₂ CH₃ N CH₃ CH H C₂H₅ C₄H₉ — 4150 CH₂ CH₃ N CH₃ CH H H 4-CH₃O—C₆H₄ — 4151 O CH₃ N CH₃ CH H c-C₃H₅ c-C₃H₅ — 4152 O CH₃ N CH₃ CH H CH₃ c-C₃H₅ — 4153 O CH₃ N CH₃ CH H C₂H₅ c-C₃H₅ — 4154 O CH₃ N CH₃ CH H C₃H₇ c-C₃H₅ — 4155 O CH₃ N CH₃ CH H C₄H₉ c-C₃H₅ — 4156 O CH₃ N CH₃ CH H CH₃ C₃H₇ — 4157 O CH₃ N CH₃ CH H C₂H₅ C₃H₇ — 4158 O CH₃ N CH₃ CH H C₃H₇ C₃H₇ — 4159 O CH₃ N CH₃ CH H C₂H₅ C₄H₉ — 4160 O CH₃ N CH₃ CH H H 4-CH₃O—C₆H₄ — 4161 CH₂ OCH₃ N OCH₃ CH H c-C₃H₅ c-C₃H₅ 120-121 4162 CH₂ OCH₃ N OCH₃ CH H CH₃ c-C₃H₅ — 4163 CH₂ OCH₃ N OCH₃ CH H C₂H₅ c-C₃H₅ — 4164 CH₂ OCH₃ N OCH₃ CH H C₃H₇ c-C₃H₅ — 4165 CH₂ OCH₃ N OCH₃ CH H C₄H₉ c-C₃H₅ — 4166 CH₂ OCH₃ N OCH₃ CH H CH₃ C₃H₇ oil 4167 CH₂ OCH₃ N OCH₃ CH H C₂H₅ C₃H₇ — 4168 CH₂ OCH₃ N OCH₃ CH H C₃H₇ C₃H₇ — 4169 CH₂ OCH₃ N OCH₃ CH H C₂H₅ C₄H₉ — 4170 CH₂ OCH₃ N OCH₃ CH H H 4-CH₃O—C₆H₄ — 4171 O OCH₃ N OCH₃ CH H c-C₃H₅ c-C₃H₅ oil 4172 O OCH₃ N OCH₃ CH H CH₃ c-C₃H₅ — 4173 O OCH₃ N OCH₃ CH H C₂H₅ c-C₃H₅ — 4174 O OCH₃ N OCH₃ CH H C₃H₇ c-C₃H₅ — 4175 O OCH₃ N OCH₃ CH H C₄H₉ c-C₃H₅ — 4176 O OCH₃ N OCH₃ CH H CH₃ C₃H₇ — 4177 O OCH₃ N OCH₃ CH H C₂H₅ C₃H₇ — 4178 O OCH₃ N OCH₃ CH H C₃H₇ C₃H₇ — 4179 O OCH₃ N OCH₃ CH H C₂H₅ C₄H₉ — 4180 O OCH₃ N OCH₃ CH H H 4-CH₃O—C₆H₄ — 4181 CH₂ OCH₃ N N(CH₃)₂ CH H c-C₃H₅ c-C₃H₅ — 4182 CH₂ OCH₃ N N(CH₃)₂ CH H CH₃ c-C₃H₅ — 4183 CH₂ OCH₃ N N(CH₃)₂ CH H C₂H₅ c-C₃H₅ — 4184 CH₂ OCH₃ N N(CH₃)₂ CH H C₃H₇ c-C₃H₅ — 4185 CH₂ OCH₃ N N(CH₃)₂ CH H C₄H₉ c-C₃H₅ — 4186 CH₂ OCH₃ N N(CH₃)₂ CH H CH₃ C₃H₇ — 4187 CH₂ OCH₃ N N(CH₃)₂ CH H C₂H₅ C₃H₇ — 4188 CH₂ OCH₃ N N(CH₃)₂ CH H C₃H₇ C₃H₇ — 4189 CH₂ OCH₃ N N(CH₃)₂ CH H C₂H₅ C₄H₉ 4190 CH₂ OCH₃ N N(CH₃)₂ CH H H 4-CH₃O—C₆H₄ — 4191 O OCH₃ N N(CH₃)₂ CH H c-C₃H₅ c-C₃H₅ — 4192 O OCH₃ N N(CH₃)₂ CH H CH₃ c-C₃H₅ — 4193 O OCH₃ N N(CH₃)₂ CH H C₂H₅ c-C₃H₅ — 4194 O OCH₃ N N(CH₃)₂ CH H C₃H₇ c-C₃H₅ — 4195 O OCH₃ N N(CH₃)₂ CH H C₄H₉ c-C₃H₅ — 4196 O OCH₃ N N(CH₃)₂ CH H CH₃ C₃H₇ — 4197 O OCH₃ N N(CH₃)₂ CH H C₂H₅ C₃H₇ — 4198 O OCH₃ N N(CH₃)₂ CH H C₃H₇ C₃H₇ — 4199 O OCH₃ N N(CH₃)₂ CH H C₂H₅ C₄H₉ — 4200 O OCH₃ N N(CH₃)₂ CH H H 4-CH₃O—C₆H₄ — 4201 CH₂ N(CH₃)₂ N OCH₃ CH H c-C₃H₅ c-C₃H₅ — 4202 CH₂ N(CH₃)₂ N OCH₃ CH H CH₃ c-C₃H₅ — 4203 CH₂ N(CH₃)₂ N OCH₃ CH H C₂H₅ c-C₃H₅ — 4204 CH₂ N(CH₃)₂ N OCH₃ CH H C₃H₇ c-C₃H₅ — 4205 CH₂ N(CH₃)₂ N OCH₃ CH H C₄H₉ c-C₃H₅ — 4206 CH₂ N(CH₃)₂ N OCH₃ CH H CH₃ C₃H₇ — 4207 CH₂ N(CH₃)₂ N OCH₃ CH H C₂H₅ C₃H₇ — 4208 CH₂ N(CH₃)₂ N OCH₃ CH H C₃H₇ C₃H₇ — 4209 CH₂ N(CH₃)₂ N OCH₃ CH H C₂H₅ C₄H₉ — 4210 CH₂ N(CH₃)₂ N OCH₃ CH H H 4-CH₃O—C₆H₄ — 4211 O N(CH₃)₂ N OCH₃ CH H c-C₃H₅ c-C₃H₅ — 4212 O N(CH₃)₂ N OCH₃ CH H CH₃ c-C₃H₅ — 4213 O N(CH₃)₂ N OCH₃ CH H C₂H₅ c-C₃H₅ — 4214 O N(CH₃)₂ N OCH₃ CH H C₃H₇ c-C₃H₅ — 4215 O N(CH₃)₂ N OCH₃ CH H C₄H₉ c-C₃H₅ — 4216 O N(CH₃)₂ N OCH₃ CH H CH₃ C₃H₇ — 4217 O N(CH₃)₂ N OCH₃ CH H C₂H₅ C₃H₇ — 4218 O N(CH₃)₂ N OCH₃ CH H C₃H₇ C₃H₇ — 4219 O N(CH₃)₂ N OCH₃ CH H C₂H₅ C₄H₉ — 4220 O N(CH₃)₂ N OCH₃ CH H H 4-CH₃O—C₆H₄ — 4221 CH₂ OCH₃ N OCH₃ CH H C₂H₅ 2-furanyl — 4222 CH₂ OCH₃ N OCH₃ CH H C₃H₇ 2-furanyl — 4223 CH₂ OCH₃ N OCH₃ CH H C₂H₅ b — 4224 CH₂ OCH₃ N OCH₃ CH H C₃H₇ b — 4225 CH₂ OCH₃ N OCH₃ CH H C₆H₅ b — 4226 CH₂ OCH₃ N OCH₃ CH H c-C₃H₅ b — 4227 CH₂ OCH₃ N OCH₃ CH H CH₃ CH═CHCH₃ — 4228 CH₂ OCH₃ N OCH₃ CH H C₃H₇ CH═CH₂ — 4229 CH₂ OCH₃ N OCH₃ CH H CH₃ C₆H₅ — 4230 CH₂ OCH₃ N OCH₃ CH H CH₃ c-C₄H₇ —

Key:

a) Where the compound is indicated as an “oil”, spectral data is below:

Example 4166 elemental analysis: calc. for C₁₉H₂₅N₅O₂ C, 64.20; H, 7.10; N, 19.70; observed C, 64.13; H,6.67; N, 19.30.

Example 4171 elemental analysis: calc. for C₂₀H₂₃N₅O₃ C, 62.98; H, 6.09; N, 18.36; observed C, 62.80; H, 6.10; N, 18.19.

b) C≡C—CH₃

The methods used in the preparation of the compounds of Table 1 may be employed in the synthesis of those compounds of Structure A in Table 5 and Table 5A. The methods employed to make the analogues bearing a benzofuran group are illustrated in the following examples.

The methods of Schemes 13 and 14 may be used to prepare many of the examples of Structure B and Structure C contained in Table 5 and Table 5A, with minor procedural modifications where necessary and use of reagents of the appropriate structure.

EXAMPLE 5001 Preparation of 9-Dicyclopropylmethyl-8-ethyl-6-(6-methyl-2,3-dihydrobenzofuran-5-yl)purine

Part A. Sodium hydride dispersion in mineral oil (5.05 g, 50% w/w, 105 mmol) was washed with hexane and dried under vacuum. DMF (100 mL) was added, the slurry was cooled to 0° C., and treated with a solution of m-cresol (10 mL, 95.6 mmol) in DMF (20 mL). The resulting mixture was allowed to stir for 1 h, then was treated with chloromethyl methyl ether (8.00 mL, 105 mmol) by syringe. The mixture was stirred overnight, then poured into ethyl acetate (200 mL). This was washed with water (3×200 mL) and brine (100 mL), and the aqueous phases were back-extracted in sequence with ethyl acetate. The extracts were combined, dried over magnesium sulfate, filtered and evaporated. The oily product was purified by elution through a plug of silica gel with 10:90 ethyl acetate-hexane. Evaporation then afforded the pure product, 3-(methoxymethoxy)toluene, as an oil (13.93 g, 91.5 mmol, 96%). TLC R_(F) 0.46 (10:90 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.17 (1H, t, J=7.7 Hz), 6.86-6.81 (3H, m), 5.17 (2H, s), 3.48 (3H, s), 2.33 (3H, s). MS (H₂O-GC/Ms): m/e 153 (60), 121 (100).

Part B. A solution of 3-(methoxymethoxy)toluene (5.00 g, 32.9 mmol) and TMEDA (5.30 mL, 35.1 mmol) in THF (50 mL) was cooled to 0° C., and treated with a hexane solution of n-butyllithium (22.0 mL, 1.6 M, 35.2 mmol). After 4 hours, the solution was cooled to −78° C., and treated dropwise with ethylene oxide (2.00 mL, 40 mmol, condensed from a lecture bottle through a cold-finger into a graduated dropping funnel). The mixture was allowed to stir and warm to ambient temperature overnight, then was poured into satd. aq. ammonium chloride solution (120 mL). This was extracted with ethyl acetate (2×120 mL), and the extracts were washed in sequence with brine, combined, dried over magnesium sulfate, filtered and evaporated. The residual oil was separated by column chromatography (10:90 ethyl acetate-hexane) to afford the desired product, 2-[2-(methoxymethoxy)-4-methylphenyl]ethanol, as a viscous liquid (2.25 g, 11.5 mmol, 35%), along with 2.50 g recovered starting material. The ¹H NMR spectrum showed regioselectivity in excess of 10:1. TLC R_(F) 0.09 (10:90 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.06 (1H, d, J=7.7 Hz), 6.92 (1H, br s), 6.78 (1H, br d, J=7.7 Hz), 5.20 (2H, s), 3.83 (2H, q, J=6.4 Hz), 3.49 (3H, s), 2.89 (2H, t, J=6.6 Hz), 2.32 (3H, s), 1.61 (1H, t, J=5.9 Hz). MS (NH₃-DCI): m/e 214 (76), 212 (100), 197 (9), 182 (30), 165 (38).

Part C. A solution of the MOM compound from Part B (1.84 g, 9.38 mmol) was dissolved in 1:1 THF-isopropanol (20 mL), and treated with HCl in dioxane (2.5 mL, 4 N, 10.0 mmol). The reaction was stirred at ambient temperature overnight. Aqueous workup gave sufficiently pure product, 2-(2-hydroxy-4-methylphenyl)ethanol.

Part D. A solution of the diol from Part C (ca. 9 mmol) and triphenylphosphine (2.83 g, 10.8 mmol) in THF (20 mL) was cooled to 0° C., and treated with diethyl azodicarboxylate (1.70 mL, 10.8 mmol) by syringe. The solution was stirred overnight, then evaporated, and the residue separated by a flash column to afford the product, 6-methyl-2,3-dihydrobenzofuran (780 mg, 5.81 mmol, 65%). TLC R_(F) 0.29 (2:98 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.07 (1H, d, J=7.4 Hz), 6.66 (1H, d, J=7.4 Hz), 6.62 (1H, s), 4.54 (2H, t, J=8.6 Hz), 3.16 (2H, t, J=8.6 Hz), 2.30 (3H, s). MS (D₂O-GC/MS): m/e 135 (100).

Part E. A solution of the above compound (780 mg) and N-bromosuccinimide (1.24 g, 6.97 mmol) in dichloroethane (10 mL) was heated to reflux overnight, then cooled, filtered and evaporated. Column chromatography (hexane, then 2:98 ethyl acetate-hexane) gave first 5-bromo-6-methylbenzofuran (270 mg, 1.27 mmol, 22%), then 5-bromo-6-methyl-2,3-dihydrobenzofuran (923 mg, 4.33 mol, 75%), both as solids. For the dihydro product: TLC R_(F) 0.35 (2:98 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 7.31 (1H, s), 6.68 (1H, s), 4.56 (2H, t, J=8.8 Hz), 3.17 (2H, t, J=8.8 Hz), 2.33 (3H, s). MS (H₂O-GC/MS): m/e 215 (76), 213 (100).

Part F. A solution of the bromide from Part E (923 mg, 4.33 mmol) in tetrahydrofuran (20 mL) was cooled to −78° C., and treated with a hexane solution of n-butyllithium (3.0 mL, 1.6 M, 4.8 mmol). After 1 hour, the reaction mixture was treated with triisopropylborate (1.00 mL, 4.33 mmol) and allowed to come to ambient temperature over 6 hrs. Then, 1 mL of 6 N aq. HCl and 3 mL water were added, and the resulting mixture was allowed to stir for 1 hr. It was poured into water (100 mL), and extracted with ethyl acetate (2×100 mL). The extracts were washed with brine (60 mL), combined, dried over sodium sulfate, filtered and evaporated to afford a solid, which was purified by trituration with hexane to give 6-methyl-2,3-dihydrobenzofuran-5-boronic acid (718 mg, 4.03 mmol, 93%).

Part G. A mixture of the boronic acid from Part F (298 mg, 1.67 mmol), 6-chloro-9-dicyclopropylmethyl-8-ethylpurine (309 mg, 1.12 mmol), 2 N aqueous sodium carbonate solution (1.7 mL, 3.4 mmol) and triphenylphosphine (61 mg, 0.233 mmol) in DME (20 mL) was degassed by repeated cycles of brief vacuum pumping followed by nitrogen purging. To this was added palladium (II) acetate (13 mg, 0.058 mmol), and the mixture was degassed again and then heated to reflux for 14 hours. It was cooled, and poured into water (100 mL). This mixture was extracted with ethyl acetate (2×100 mL), and the extracts were washed in sequence with brine (60 mL), combined, dried over sodium sulfate, filtered and evaporated. The residual material was separated by column chromatography (silica gel, 20:80 ethyl acetate-hexane) to afford the title product as a solid. This was recrystallized to purity from ether (253 mg, 0.77 mmol, 69%). m.p. 147-148° C. TLC R_(F) 0.18 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.88 (1H, s), 7.60 (1H, s), 6.77 (1H, s), 4.61 (2H, t, J=8.6 Hz), 3.44 (1H, v br), 3.24 (2H, t, J=8.6 Hz), 2.94 (2H, br), 2.44 (3H, s), 2.03 (2H, v br), 1.45 (3H, br t, J=6 Hz), 0.89-0.79 (2H, m), 0.58 (2H, br), 0.50-0.40 (2H, m), 0.27-0.17 (2H, m). MS (NH₃-CI): m/e 377 (4), 376 (27), 375 (100). Analysis calc'd for C₂₃H₂₆N₄O: C, 73.77; H, 7.01; N, 14.96; found: C, 73.69; H, 7.08; N, 14.40.

EXAMPLES 5201, 5231 and 5232 Preparation of 9-dicyclopropylmethyl-8-ethyl-6-(6-methylbenzofuran-5-yl)purine, 6-(2-bromo-6-methylbenzofuran-5-yl)-9-dicyclopropylmethyl-8-ethylpurine and 6-(7-bromo-6-methyl-2,3-dihydrobenzofuran-5-yl)-9-dicyclopropylmethyl-8-ethylpurine

A solution of the compound of Example 5001 (250 mg, 0.668 mmol) and N-bromosuccinimide (119 mg, 0.669 mmol) in 1,2-dichloroethane (10 mL) was heated to reflux for 12 hours, then cooled and evaporated. The resulting mixture was taken up in ether, filtered and evaporated, and the residual material was separated by flash chromatography (silica gel, 20:80 ethyl acetate-hexane) to afford, in order, the following three products: 6-(2-Bromo-6-methylbenzofuran-5-yl)-9-dicyclopropylmethyl-8-ethylpurine: m.p. 177-178° C. TLC R_(F) 0.23 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.92 (1H, s), 7.85 (1H, s), 7.42 (1H, s), 6.74 (1H, s), 4.15 (1H, v br), 2.97 (2H, v br), 2.54 (3H, s), 2.00 (2H, v br), 1.44 (3H, br t, J=7 Hz), 0.90-0.80 (2H, m), 0.63-0.53 (2H, m), 0.50-0.40 (2H, m), 0.26-0.16 (2H, m). MS (NH₃-CI): m/e calc'd for C₂₃H₂₄BrN₄O: 451.1133, found 451.1132; 455 (3), 454 (25), 453 (99), 452 (31), 451 (100). 9-Dicyclopropylmethyl-8-ethyl-6-(6-methylbenzofuran-5-yl)purine: m.p. 139-141° C. TLC R_(F) 0.16 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.92 (1H, s), 7.95 (1H_(,) s), 7.60 (1H, d, J=2.2 Hz), 7.48 (1H, d, J=0.7 Hz), 6.78 (1H, dd, J=2.2, 0.7 Hz), 4.40 (1H, v br), 2.97 (2H, v br), 2.56 (3H, s), 2.04 (2H, v br), 1.44 (3H, br t, J=7 Hz), 0.90-0.80 (2H, m), 0.62-0.52 (2H, m), 0.51-0.41 (2H, m), 0.29-0.18 (2H, m). MS (NH₃-CI): m/e calc'd for C₂₃H₂₅N₄O: 373.2028, found 373.2033; 375 (3), 374 (26), 373 (100). 6-(7-Bromo-6-methyl-2,3-dihydrobenzofuran-5-yl)-9-dicyclopropylmethyl-8-ethylpurine: m.p. 179-180° C. TLC R_(F) 0.04 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): d 8.89 (1H, s), 7.47 (1H, s), 4.73 (2H, t, J=8.6 Hz), 3.80 (1H, v br), 3.37 (2H, t, J=8.6 Hz), 2.95 (2H, v br), 2.44 (3H, s), 1.44 (3H, br t, J=7 Hz), 0.89-0.79 (2H, m), 0.61-0.52 (2H, m), 0.51-0.41 (2H, m), 0.28-0.18 (2H, m). MS (NH₃-CI): m/e calc'd for C₂₃H₂₆BrN₄O: 453.1290, found 453.1285; 455 453 (100).

TABLE 5

(A) (B)

(C) Ex. m.p., No. X R³ R⁴ a b c R^(1a) R^(1b) ° C. 5001 CH₂ H CH₃ CH₂ CH₂ O c-C₃H₅ c-C₃H₅ 147-148 5002 CH₂ H CH₃ CH₂ CH₂ O H 4-(CH₃O)—C₆H₄ — 5003 CH₂ H CH₃ CH₂ CH₂ O CH₃ c-C₃H₅ — 5004 CH₂ H CH₃ CH₂ CH₂ O C₂H₅ c-C₃H₅ — 5005 CH₂ H CH₃ CH₂ CH₂ O C₃H₇ c-C₃H₅ — 5006 CH₂ H CH₃ CH₂ CH₂ O C₄H₉ c-C₃H₅ — 5007 CH₂ H CH₃ CH₂ CH₂ O C₂H₅ C₃H₇ — 5008 CH₂ H CH₃ CH₂ CH₂ O C₂H₅ C₄H₉ — 5009 CH₂ H CH₃ CH₂ CH₂ O C₃H₇ C₃H₇ — 5010 CH₂ H CH₃ CH₂ CH₂ O CH₃ C₃H₇ — 5011 CH₂ H CH₃ O CH₂ O c-C₃H₅ c-C₃H₅ 168-169 5012 CH₂ H CH₃ O CH₂ O H 4-(CH₃O)—C₆H₄ — 5013 CH₂ H CH₃ O CH₂ O CH₃ c-C₃H₅ — 5014 CH₂ H CH₃ O CH₂ O C₂H₅ c-C₃H₅ — 5015 CH₂ H CH₃ O CH₂ O C₃H₇ c-C₃H₅ — 5016 CH₂ H CH₃ O CH₂ O C₄H₉ c-C₃H₅ — 5017 CH₂ H CH₃ O CH₂ O C₂H₅ C₃H₇ — 5018 CH₂ H CH₃ O CH₂ O C₂H₅ C₄H₉ — 5019 CH₂ H CH₃ O CH₂ O C₃H₇ C₃H₇ — 5020 CH₂ H CH₃ O CH₂ O CH₃ C₃H₇ — 5021 CH₂ H CH₃ O CH₂ CH₂ c-C₃H₅ c-C₃H₅ — 5022 CH₂ H CH₃ O CH₂ CH₂ H 4-(CH₃O)—C₆H₄ — 5023 CH₂ H CH₃ O CH₂ CH₂ CH₃ c-C₃H₅ — 5024 CH₂ H CH₃ O CH₂ CH₂ C₂H₅ c-C₃H₅ — 5025 CH₂ H CH₃ O CH₂ CH₂ C₃H₇ c-C₃H₅ — 5026 CH₂ H CH₃ O CH₂ CH₂ C₄H₉ c-C₃H₅ — 5027 CH₂ H CH₃ O CH₂ CH₂ C₂H₅ C₃H₇ — 5028 CH₂ H CH₃ O CH₂ CH₂ C₂H₅ C₄H₉ — 5029 CH₂ H CH₃ O CH₂ CH₂ C₃H₇ C₃H₇ — 5030 CH₂ H CH₃ O CH₂ CH₂ CH₃ C₃H₇ — 5031 CH₂ H CH₃ CH₂ O CH₂ c-C₃H₅ c-C₃H₅ — 5032 CH₂ H CH₃ CH₂ O CH₂ H 4-(CH₃O)—C₆H₄ — 5033 CH₂ H CH₃ CH₂ O CH₂ CH₃ c-C₃H₅ — 5034 CH₂ H CH₃ CH₂ O CH₂ C₂H₅ c-C₃H₅ — 5035 CH₂ H CH₃ CH₂ O CH₂ C₃H₇ c-C₃H₅ — 5036 CH₂ H CH₃ CH₂ O CH₂ C₄H₉ c-C₃H₅ — 5037 CH₂ H CH₃ CH₂ O CH₂ C₂H₅ C₃H₇ — 5038 CH₂ H CH₃ CH₂ O CH₂ C₂H₅ C₄H₉ — 5039 CH₂ H CH₃ CH₂ O CH₂ C₃H₇ C₃H₇ — 5040 CH₂ H CH₃ CH₂ O CH₂ CH₃ C₃H₇ — 5041 CH₂ H Cl CH₂ CH₂ O c-C₃H₅ c-C₃H₅ — 5042 CH₂ H Cl CH₂ CH₂ O H 4-(CH3O)-C6H4 — 5043 CH₂ H Cl CH₂ CH₂ O CH₃ c-C₃H₅ — 5044 CH₂ H Cl CH₂ CH₂ O C₂H₅ c-C₃H₅ — 5045 CH₂ H Cl CH₂ CH₂ O C₃H₇ c-C₃H₅ — 5046 CH₂ H Cl CH₂ CH₂ O C₄H₉ c-C₃H₅ — 5047 CH₂ H Cl CH₂ CH₂ O C₂H₅ C₃H₇ — 5048 CH₂ H Cl CH₂ CH₂ O C₂H₅ C₄H₉ — 5049 CH₂ H Cl CH₂ CH₂ O C₃H₇ C₃H₇ — 5050 CH₂ H Cl CH₂ CH₂ O CH₃ C₃H₇ — 5051 CH₂ H Cl O CH₂ O c-C₃H₅ c-C₃H₅ — 5052 CH₂ H Cl O CH₂ O H 4-(CH₃O)—C₆H₄ — 5053 CH₂ H Cl O CH₂ O CH₃ c-C₃H₅ — 5054 CH₂ H Cl O CH₂ O C₂H₅ c-C₃H₅ — 5055 CH₂ H Cl O CH₂ O C₃H₇ c-C₃H₅ — 5056 CH₂ H Cl O CH₂ O C₄H₉ c-C₃H₅ — 5057 CH₂ H Cl O CH₂ O C₂H₅ C₃H₇ — 5058 CH₂ H Cl O CH₂ O C₂H₅ C₄H₉ — 5059 CH₂ H Cl O CH₂ O C₃H₇ C₃H₇ — 5060 CH₂ H Cl O CH₂ O CH₃ C₃H₇ — 5061 O H CH₃ CH₂ CH₂ O c-C₃H₅ c-C₃H₅ — 5062 O H CH₃ CH₂ CH₂ O H 4-(CH₃O)—C₆H₄ — 5063 O H CH₃ CH₂ CH₂ O CH₃ c-C₃H₅ — 5064 O H CH₃ CH₂ CH₂ O C₂H₅ c-C₃H₅ — 5065 O H CH₃ CH₂ CH₂ O C₃H₇ c-C₃H₅ — 5066 O H CH₃ CH₂ CH₂ O C₄H₉ c-C₃H₅ — 5067 O H CH₃ CH₂ CH₂ O C₂H₅ C₃H₇ — 5068 O H CH₃ CH₂ CH₂ O C₂H₅ C₄H₉ — 5069 O H CH₃ CH₂ CH₂ O C₃H₇ C₃H₇ — 5070 O H CH₃ CH₂ CH₂ O CH₃ C₃H₇ — 5071 O H CH₃ O CH₂ O c-C₃H₅ c-C₃H₅ — 5072 O H CH₃ O CH₂ O H 4-(CH₃O)—C₆H₄ — 5073 O H CH₃ O CH₂ O CH₃ c-C₃H₅ — 5074 O H CH₃ O CH₂ O C₂H₅ c-C₃H₅ — 5075 O H CH₃ O CH₂ O C₃H₇ c-C₃H₅ — 5076 O H CH₃ O CH₂ O C₄H₉ c-C₃H₅ — 5077 O H CH₃ O CH₂ O C₂H₅ C₃H₇ — 5078 O H CH₃ O CH₂ O C₂H₅ C₄H₉ — 5079 O H CH₃ O CH₂ O C₃H₇ C₃H₇ — 5080 O H CH₃ O CH₂ O C₃H₇ C₃H₇ — 5081 O H Cl CH₂ CH₂ O c-C₃H₅ c-C₃H₅ — 5082 O H Cl CH₂ CH₂ O H 4-(CH₃O)—C₆H₄ — 5083 O H Cl CH₂ CH₂ O CH₃ c-C₃H₅ — 5084 O H Cl CH₂ CH₂ O C₂H₅ c-C₃H₅ — 5085 O H Cl CH₂ CH₂ O C₃H₇ c-C₃H₅ — 5086 O H Cl CH₂ CH₂ O C₄H₉ c-C₃H₅ — 5087 O H Cl CH₂ CH₂ O C₂H₅ C₃H₇ — 5088 O H Cl CH₂ CH₂ O C₂H₅ C₄H₉ — 5089 O H Cl CH₂ CH₂ O C₃H₇ C₃H₇ — 5090 O H Cl CH₂ CH₂ O CH₃ C₃H₇ — 5091 O H Cl O CH₂ O c-C₃H₅ c-C₃H₅ — 5092 O H Cl O CH₂ O H 4-(CH₃O)—C₆H₄ — 5093 O H Cl O CH₂ O CH₃ c-C₃H₅ — 5094 O H Cl O CH₂ O C₂H₅ c-C₃H₅ — 5095 O H Cl O CH₂ O C₃H₇ c-C₃H₅ — 5096 O H Cl O CH₂ O C₄H₉ c-C₃H₅ — 5097 O H Cl O CH₂ O C₂H₅ C₃H₇ — 5098 O H Cl O CH₂ O C₂H₅ C₄H₉ — 5099 O H Cl O CH₂ O C₃H₇ C₃H₇ — 5100 O H Cl O CH₂ O C₃ C₃H₇ — 5101 CH₂ CH₃ CH₃ CH₂ CH₂ O c-C₃H₅ c-C₃H₅ — 5102 CH₂ CH₃ CH₃ CH₂ CH₂ O H 4-(CH₃O)—C₆H₄ — 5103 CH₂ CH₃ CH₃ CH₂ CH₂ O CH₃ c-C₃H₅ — 5104 CH₂ CH₃ CH₃ CH₂ CH₂ O C₂H₅ c-C₃H₅ — 5105 CH₂ CH₃ CH₃ CH₂ CH₂ O C₃H₇ c-C₃H₅ — 5106 CH₂ CH₃ CH₃ CH₂ CH₂ O C₄H₉ c-C₃H₅ — 5107 CH₂ CH₃ CH₃ CH₂ CH₂ O C₂H₅ C₃H₇ — 5108 CH₂ CH₃ CH₃ CH₂ CH₂ O C₂H₅ C₄H₉ — 5109 CH₂ CH₃ CH₃ CH₂ CH₂ O C₃H₇ C₃H₇ — 5110 CH₂ CH₃ CH₃ CH₂ CH₂ O CH₃ C₃H₇ — 5111 CH₂ H Cl O C═O NH c-C₃H₅ c-C₃H₅ — 5112 CH₂ H Cl O C═O NH H 4-(CH₃O)—C₆H₄ — 5113 CH₂ H Cl O C═O NH CH₃ c-C₃H₅ — 5114 CH₂ H Cl O C═O NH C₂H₅ c-C₃H₅ — 5115 CH₂ H Cl O C═O NH C₃H₇ c-C₃H₅ — 5116 CH₂ H Cl O C═O NH C₄H₉ c-C₃H₅ — 5117 CH₂ H Cl O C═O NH C₂H₅ C₃H₇ — 5118 CH₂ H Cl O C═O NH C₂H₅ C₄H₉ — 5119 CH₂ H Cl O C═O NH C₃H₇ C₃H₇ — 5120 CH₂ H Cl O C═O NH CH₃ C₃H₇ — 5121 CH₂ H Cl O C═O NCH₃ c-C₃H₅ c-C₃H₅ — 5122 CH₂ H Cl O C═O NCH₃ H 4-(CH₃O)—C₆H₄ — 5123 CH₂ H Cl O C═O NCH₃ CH₃ c-C₃H₅ — 5124 CH₂ H Cl O C═O NCH₃ C₂H₅ c-C₃H₅ — 5125 CH₂ H Cl O C═O NCH₃ C₃H₇ c-C₃H₅ — 5126 CH₂ H Cl O C═O NCH₃ C₄H₉ c-C₃H₅ — 5127 CH₂ H Cl O C═O NCH₃ C₂H₅ C₃H₇ — 5128 CH₂ H Cl O C═O NCH₃ C₂H₅ C₄H₉ — 5129 CH₂ H Cl O C═O NCH₃ C₃H₇ C₃H₇ — 5130 CH₂ H Cl O C═O NCH₃ CH₃ C₃H₇ — 5131 CH₂ H Cl O CCH₃ N c-C₃H₅ c-C₃H₅ — 5132 CH₂ H Cl O CCH₃ N H 4-(CH₃O)—C₆H₄ — 5133 CH₂ H Cl O CCH₃ N CH₃ c-C₃H₅ — 5134 CH₂ H Cl O CCH₃ N C₂H₅ c-C₃H₅ — 5135 CH₂ H Cl O CCH₃ N C₃H₇ c-C₃H₅ — 5136 CH₂ H Cl O CCH₃ N C₄H₉ c-C₃H₅ — 5137 CH₂ H Cl O CCH₃ N C₂H₅ C₃H₇ — 5138 CH₂ H Cl O CCH₃ N C₂H₅ C₄H₉ — 5139 CH₂ H Cl O CCH₃ N C₃H₇ C₃H₇ — 5140 CH₂ H Cl O CCH₃ N CH₃ C₃H₇ — 5141 CH₂ H Cl O C═O NC₂H₅ c-C₃H₅ c-C₃H₅ — 5142 CH₂ H Cl O C═O NC₂H₅ H 4-(CH₃O)—C₆H₄ — 5143 CH₂ H Cl O C═O NC₂H₅ CH₃ c-C₃H₅ — 5144 CH₂ H Cl O C═O NC₂H₅ C₂H₅ c-C₃H₅ — 5145 CH₂ H Cl O C═O NC₂H₅ C₃H₇ c-C₃H₅ — 5146 CH₂ H Cl O C═O NC₂H₅ C₄H₉ c-C₃H₅ — 5147 CH₂ H Cl O C═O NC₂H₅ C₂H₅ C₃H₇ — 5148 CH₂ H Cl O C═O NC₂H₅ C₂H₅ C₄H₉ — 5149 CH₂ H Cl O C═O NC₂H₅ C₃H₇ C₃H₇ — 5150 CH₂ H Cl O C═O NC₂H₅ CH₃ C₃H₇ — 5151 CH₂ H Cl O C═O O c-C₃H₅ c-C₃H₅ — 5152 CH₂ H Cl O C═O O H 4-(CH₃O)—C₆H₄ — 5153 CH₂ H Cl O C═O O CH₃ c-C₃H₅ — 5154 CH₂ H Cl O C═O O C₂H₅ c-C₃H₅ — 5155 CH₂ H Cl O C═O O C₃H₇ c-C₃H₅ — 5156 CH₂ H Cl O C═O O C₄H₉ c-C₃H₅ — 5157 CH₂ H Cl O C═O O C₂H₅ C₃H₇ — 5158 CH₂ H Cl O C═O O C₂H₅ C₄H₉ — 5159 CH₂ H Cl O C═O O C₃H₇ C₃H₇ — 5160 CH₂ H Cl O C═O O CH₃ C₃H₇ — 5161 CH₂ H Cl O CH₂CH₂ O c-C₃H₅ c-C₃H₅ — 5162 CH₂ H Cl O CH₂CH₂ O H 4-(CH₃O)—C₆H₄ — 5163 CH₂ H Cl O CH₂CH₂ O CH₃ c-C₃H₅ — 5164 CH₂ H Cl O CH₂CH₂ O C₂H₅ c-C₃H₅ — 5165 CH₂ H Cl O CH₂CH₂ O C₃H₇ c-C₃H₅ — 5166 CH₂ H Cl O CH₂CH₂ O C₄H₉ c-C₃H₅ — 5167 CH₂ H Cl O CH₂CH₂ O C₂H₅ C₃H₇ — 5168 CH₂ H Cl O CH₂CH₂ O C₂H₅ C₄H₉ — 5169 CH₂ H Cl O CH₂CH₂ O C₃H₇ C₃H₇ — 5170 CH₂ H Cl O CH₂CH₂ O CH₃ C₃H₇ — 5171 CH₂ H CH₃ O C═O O c-C₃H₅ c-C₃H₅ — 5172 CH₂ H CH₃ O C═O O H 4-(CH₃O)—C₆H₄ — 5173 CH₂ H CH₃ O C═O O CH₃ c-C₃H₅ — 5174 CH₂ H CH₃ O C═O O C₂H₅ c-C₃H₅ — 5175 CH₂ H CH₃ O C═O O C₃H₇ c-C₃H₅ — 5176 CH₂ H CH₃ O C═O O C₄H₉ c-C₃H₅ — 5177 CH₂ H CH₃ O C═O O C₂H₅ C₃H₇ — 5178 CH₂ H CH₃ O C═O O C₂H₅ C₄H₉ — 5179 CH₂ H CH₃ O C═O O C₃H₇ C₃H₇ — 5180 CH₂ H CH₃ O C═O O CH₃ C₃H₇ — 5181 CH₂ H CH₃ O CH₂CH₂ O c-C₃H₅ c-C₃H₅ — 5182 CH₂ H CH₃ O CH₂CH₂ O H 4-(CH₃O)—C₆H₄ — 5183 CH₂ H CH₃ O CH₂CH₂ O CH₃ c-C₃H₅ — 5184 CH₂ H CH₃ O CH₂CH₂ O C₂H₅ c-C₃H₅ — 5185 CH₂ H CH₃ O CH₂CH₂ O C₃H₇ c-C₃H₅ — 5186 CH₂ H CH₃ O CH₂CH₂ O C₄H₉ c-C₃H₅ — 5187 CH₂ H CH₃ O CH₂CH₂ O C₂H₅ C₃H₇ — 5188 CH₂ H CH₃ O CH₂CH₂ O C₂H₅ C₄H₉ — 5189 CH₂ H CH₃ O CH₂CH₂ O C₃H₇ C₃H₇ — 5190 CH₂ H CH₃ O CH₂CH₂ O CH₃ C₃H₇ — 5191 CH₂ H Cl O CH₂CH₂ NCH₃ c-C₃H₅ c-C₃H₅ — 5192 CH₂ H Cl O CH₂CH₂ NCH₃ H 4-(CH₃O)—C₆H₄ — 5193 CH₂ H Cl O CH₂CH₂ NCH₃ CH₃ c-C₃H₅ — 5194 CH₂ H Cl O CH₂CH₂ NCH₃ C₂H₅ c-C₃H₅ — 5195 CH₂ H Cl O CH₂CH₂ NCH₃ C₃H₇ c-C₃H₅ — 5196 CH₂ H Cl O CH₂CH₂ NCH₃ C₄H₉ c-C₃H₅ — 5197 CH₂ H Cl O CH₂CH₂ NCH₃ C₂H₅ C₃H₇ — 5198 CH₂ H Cl O CH₂CH₂ NCH₃ C₂H₅ C₄H₉ — 5199 CH₂ H Cl O CH₂CH₂ NCH₃ C₃H₇ C₃H₇ — 5200 CH₂ H Cl O CH₂CH₂ NCH₃ CH₃ C₃H₇ — 5201 CH₂ H CH₃ CH CH O c-C₃H₅ c-C₃H₅ 139-141 5202 CH₂ H CH₃ CH CH O H 4-(CH₃O)—C₆H₄ — 5203 CH₂ H CH₃ CH CH O CH₃ c-C₃H₅ — 5204 CH₂ H CH₃ CH CH O C₂H₅ c-C₃H₅ — 5205 CH₂ H CH₃ CH CH O C₃H₇ c-C₃H₅ — 5206 CH₂ H CH₃ CH CH O C₄H₉ c-C₃H₅ — 5207 CH₂ H CH₃ CH CH O C₂H₅ C₃H₇ — 5208 CH₂ H CH₃ CH CH O C₂H₅ C₄H₉ — 5209 CH₂ H CH₃ CH CH O C₃H₇ C₃H₇ — 5210 CH₂ H CH₃ CH CH O CH₃ C₃H₇ — 5211 CH₂ H Cl CH CH O c-C₃H₅ c-C₃H₅ — 5212 CH₂ H Cl CH CH O H 4-(CH₃O)—C₆H₄ — 5213 CH₂ H Cl CH CH O CH₃ c-C₃H₅ — 5214 CH₂ H Cl CH CH O C₂H₅ c-C₃H₅ — 5215 CH₂ H Cl CH CH O C_(3 H) ₇ c-C₃H₅ — 5216 CH₂ H Cl CH CH O C₄H₉ c-C₃H₅ — 5217 CH₂ H Cl CH CH O C₂H₅ C₃H₇ — 5218 CH₂ H Cl CH CH O C₂H₅ C₄H₉ — 5219 CH₂ H Cl CH CH O C₃H₇ C₃H₇ — 5220 CH₂ H Cl CH CH O CH₃ C₃H₇ — 5221 CH₂ H CH₃ CH CHCH CH c-C₃H₅ c-C₃H₅ — 5222 CH₂ H CH₃ CH CHCH CH H 4-(CH₃O)—C₆H₄ — 5223 CH₂ H CH₃ CH CHCH CH CH₃ c-C₃H₅ — 5224 CH₂ H CH₃ CH CHCH CH C₂H₅ c-C₃H₅ — 5225 CH₂ H CH₃ CH CHCH CH C₃H₇ c-C₃H₅ — 5226 CH₂ H CH₃ CH CHCH CH C₄H₉ c-C₃H₅ — 5227 CH₂ H CH₃ CH CHCH CH C₂H₅ C₃H₇ — 5228 CH₂ H CH₃ CH CHCH CH C₂H₅ C₄H₉ — 5229 CH₂ H CH₃ CH CHCH CH C₃H₇ C₃H₇ — 5230 CH₂ H CH₃ CH CHCH CH CH₃ C₃H₇ — 5231 CH₂ H CH₃ CH CBr O c-C₃H₅ c-C₃H₅ 177-178 5232 CH₂ H CH₃ CH₂ CH₂ O c-C₃H₅ c-C₃H₅ 179-180 5233 CH₂ H CH₃ CH CCH₃ O c-C₃H₅ c-C₃H₅ — 5234 CH₂ H CH₃ CH₂ CH₂ O c-C₃H₅ c-C₃H₅ — 5235 CH₂ H CH₃ CH CSCH₃ O c-C₃H₅ c-C₃H₅ — 5236 CH₂ H CH₃ CH₂ CH₂ O c-C₃H₅ c-C₃H₅ —

TABLE 5A

(A)

(B)

(C) Ex. m.p., No. X R¹² a b c R^(1a) R^(1b) ° C. 5232 CH₂ Br CH₂ CH₂ O c-C₃H₅ c-C₃H₅ 179-180 5234 CH₂ CN CH₂ CH₂ O c-C₃H₅ c-C₃H₅ — 5236 CH₂ SCH₃ CH₂ CH₂ O c-C₃H₅ c-C₃H₅ —

The methods used in the preparation of the compounds of Table 1 may be used for the compounds of Structure A of Table 6. For example, replacing variously-substituted pentaatomic heteroaryl boronic acids, for benzeneboronic acids in the palladium-catalyzed aryl cross-coupling method (see Examples 35 or 831) will afford the desired 6-heteroarylpurine compounds.

The methods of Schemes 13 and 14 may be used to prepare many of the examples of Structure B and Structure C contained in Table 6, with minor procedural modifications where necessary and use. of reagents of the appropriate structure.

TABLE 6

(A) (B)

(C) m.p. Ex. No. X R³ a b c d R^(1a) R^(1b) ° C.^(a) 6001 CH₂ H CCH₃ N O CCH₃ c-C₃H₅ c-C₃H₅ oil 6002 CH₂ H CCH₃ N O CCH₃ CH₃ c-C₃H₅ — 6003 CH₂ H CCH₃ N O CCH₃ C₂H₅ c-C₃H₅ — 6004 CH₂ H CCH₃ N O CCH₃ C₃H₇ c-C₃H₅ — 6005 CH₂ H CCH₃ N O CCH₃ C₄H₉ c-C₃H₅ — 6006 CH₂ H CCH₃ N O CCH₃ CH₃ C₃H₇ — 6007 CH₂ H CCH₃ N O CCH₃ C₂H₅ C₃H₇ — 6008 CH₂ H CCH₃ N O CCH₃ C₃H₇ C₃H₇ — 6009 CH₂ H CCH₃ N O CCH₃ C₂H₅ C₄H₉ — 6010 CH₂ H CCH₃ N O CCH₃ H 4-CH₃O—C₆H₄ — 6011 O H CCH₃ N O CCH₃ c-C₃H₅ c-C₃H₅ — 6012 O H CCH₃ N O CCH₃ CH₃ c-C₃H₅ — 6013 O H CCH₃ N O CCH₃ C₂H₅ c-C₃H₅ — 6014 O H CCH₃ N O CCH₃ C₃H₇ c-C₃H₅ — 6015 O H CCH₃ N O CCH₃ C₄H₉ c-C₃H₅ — 6016 O H CCH₃ N O CCH₃ CH₃ C₃H₇ — 6017 O H CCH₃ N O CCH₃ C₂H₅ C₃H₇ — 6O18 O H CCH₃ N O CCH₃ C₃H₇ C₃H₇ — 6019 O H CCH₃ N O CCH₃ C₂H₅ C₄H₉ — 6020 O H CCH₃ N O CCH₃ H 4-CH₃O—C₆H₄ — 6021 CH₂ CH₃ CCH₃ N O CCH₃ c-C₃H₅ c-C₃H₅ — 6022 CH₂ CH₃ CCH₃ N O CCH₃ CH₃ c-C₃H₅ — 6023 CH₂ CH₃ CCH₃ N O CCH₃ C₂H₅ c-C₃H₅ — 6024 CH₂ CH₃ CCH₃ N O CCH₃ C₃H₇ c-C₃H₅ — 6025 CH₂ CH₃ CCH₃ N O CCH₃ C₄H₉ c-C₃H₅ — 6026 CH₂ CH₃ CCH₃ N O CCH₃ CH₃ C₃H₇ — 6027 CH₂ CH₃ CCH₃ N O CCH₃ C₂H₅ C₃H₇ — 6028 CH₂ CH₃ CCH₃ N O CCH₃ C₃H₇ C₃H₇ — 6029 CH₂ CH₃ CCH₃ N O CCH₃ C₂H₅ C₄H₉ — 6030 CH₂ CH₃ CCH₃ N O CCH₃ H 4-CH₃O—C₆H₄ — 6031 CH₂ H CCH₃ N NCH₃ CCH₃ c-C₃H₅ c-C₃H₅ — 6032 CH₂ H CCH₃ N NCH₃ CCH₃ CH₃ c-C₃H₅ — 6033 CH₂ H CCH₃ N NCH₃ CCH₃ C₂H₅ c-C₃H₅ — 6034 CH₂ H CCH₃ N NCH₃ CCH₃ C₃H₇ c-C₃H₅ — 6035 CH₂ H CCH₃ N NCH₃ CCH₃ C₄H₉ c-C₃H₅ — 6036 CH₂ H CCH₃ N NCH₃ CCH₃ CH₃ C₃H₇ — 6037 CH₂ H CCH₃ N NCH₃ CCH₃ C₂H₅ C₃H₇ — 6038 CH₂ H CCH₃ N NCH₃ CCH₃ C₃H₇ C₃H₇ — 6039 CH₂ H CCH₃ N NCH₃ CCH₃ C₂H₅ C₄H₉ — 6040 CH₂ H CCH₃ N NCH₃ CCH₃ H 4-CH₃O—C₆H₄ — 6041 O H CCH₃ N NCH₃ CCH₃ c-C₃H₅ c-C₃H₅ — 6042 O H CCH₃ N NCH₃ CCH₃ CH₃ c-C₃H₅ — 6043 O H CCH₃ N NCH₃ CCH₃ C₂H₅ c-C₃H₅ — 6044 O H CCH₃ N NCH₃ CCH₃ C₃H₇ c-C₃H₅ — 6045 O H CCH₃ N NCH₃ CCH₃ C₄H₉ c-C₃H₅ — 6046 O H CCH₃ N NCH₃ CCH₃ CH₃ C₃H₇ — 6047 O H CCH₃ N NCH₃ CCH₃ C₂H₅ C₃H₇ — 6048 O H CCH₃ N NCH₃ CCH₃ C₃H₇ C₃H₇ — 6049 O H CCH₃ N NCH₃ CCH₃ C₂H₅ C₄H₉ — 6050 O H CCH₃ N NCH₃ CCH₃ H 4-CH₃O—C₆H₄ — 6051 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ c-C₃H₅ c-C₃H₅ — 6052 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ CH₃ c-C₃H₅ — 6053 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₂H₅ c-C₃H₅ — 6054 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₃H₇ c-C₃H₅ — 6055 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₄H₉ c-C₃H₅ — 6056 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ CH₃ C₃H₇ — 6057 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₂H₅ C₃H₇ — 6058 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₃H₇ C₃H₇ — 6059 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ C₂H₅ C₄H₉ — 6060 CH₂ CH₃ CCH₃ N NCH₃ CCH₃ H 4-CH₃O—C₆H₄ — 6061 CH₂ H CCH₃ N NC₂H₅ CCH₃ c-C₃H₅ c-C₃H₅ — 6062 CH₂ H CCH₃ N NC₂H₅ CCH₃ CH₃ c-C₃H₅ — 6063 CH₂ H CCH₃ N NC₂H₅ CCH₃ C₂H₅ c-C₃H₅ — 6064 CH₂ H CCH₃ N NC₂H₅ CCH₃ C₃H₇ c-C₃H₅ — 6065 CH₂ H CCH₃ N NC₂H₅ CCH₃ C₄H₉ c-C₃H₅ — 6066 CH₂ H CCH₃ N NC₂H₅ CCH₃ CH₃ C₃H₇ — 6067 CH₂ H CCH₃ N NC₂H₅ CCH₃ C₂H₅ C₃H₇ — 6068 CH₂ H CCH₃ N NC₂H₅ CCH₃ C₃H₇ C₃H₇ — 6069 CH₂ H CCH₃ N NC₂H₅ CCH₃ C₂H₅ C₄H₉ — 6070 CH₂ H CCH₃ N NC₂H₅ CCH₃ H 4-CH₃O—C₆H₄ — 6071 O H CCH₃ N NC₂H₅ CCH₃ c-C₃H₅ c-C₃H₅ — 6072 O H CCH₃ N NC₂H₅ CCH₃ CH₃ c-C₃H₅ — 6073 O H CCH₃ N NC₂H₅ CCH₃ C₂H₅ c-C₃H₅ — 6074 O H CCH₃ N NC₂H₅ CCH₃ C₃H₇ c-C₃H₅ — 6075 O H CCH₃ N NC₂H₅ CCH₃ C₄H₉ c-C₃H₅ — 6076 O H CCH₃ N NC₂H₅ CCH₃ CH₃ C₃H₇ — 6077 O H CCH₃ N NC₂H₅ CCH₃ C₂H₅ C₃H₇ — 6078 O H CCH₃ N NC₂H₅ CCH₃ C₃H₇ C₃H₇ — 6079 O H CCH₃ N NC₂H₅ CCH₃ C₂H₅ C₄H₉ — 6080 O H CCH₃ N NC₂H₅ CCH₃ H 4-CH₃O—C₆H₄ — 6081 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ c-C₃H₅ c-C₃H₅ — 6082 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ CH₃ c-C₃H₅ — 6083 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ C₂H₅ c-C₃H₅ — 6084 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ C₃H₇ c-C₃H₅ — 6085 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ C₄H₉ c-C₃H₅ — 6086 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ CH₃ C₃H₇ — 6087 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ C₂H₅ C₃H₇ — 6088 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ C₃H₇ C₃H₇ — 6089 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ C₂H₅ C₄H₉ — 6090 CH₂ CH₃ CCH₃ N NC₂H₅ CCH₃ H 4-CH₃O—C₆H₄ — 6091 CH₂ H CCH₃ N CCH₃ NCH₃ c-C₃H₅ c-C₃H₅ — 6092 CH₂ H CCH₃ N CCH₃ NCH₃ CH₃ c-C₃H₅ — 6093 CH₂ H CCH₃ N CCH₃ NCH₃ C₂H₅ c-C₃H₅ — 6094 CH₂ H CCH₃ N CCH₃ NCH₃ C₃H₇ c-C₃H₅ — 6095 CH₂ H CCH₃ N CCH₃ NCH₃ C₄H₉ c-C₃H₅ — 6096 CH₂ H CCH₃ N CCH₃ NCH₃ CH₃ C₃H₇ — 6097 CH₂ H CCH₃ N CCH₃ NCH₃ C₂H₅ C₃H₇ — 6098 CH₂ H CCH₃ N CCH₃ NCH₃ C₃H₇ C₃H₇ — 6099 CH₂ H CCH₃ N CCH₃ NCH₃ C₂H₅ C₄H₉ — 6100 CH₂ H CCH₃ N CCH₃ NCH₃ H 4-CH₃O—C₆H₄ — 6101 CH₂ H CCH₃ N NC₆H₅ CCH₃ c-C₃H₅ c-C₃H₅ — 6102 CH₂ H CCH₃ N NC₆H₅ CCH₃ CH₃ c-C₃H₅ — 6103 CH₂ H CCH₃ N NC₆H₅ CCH₃ C₂H₅ c-C₃H₅ — 6104 CH₂ H CCH₃ N NC₆H₅ CCH₃ C₃H₇ c-C₃H₅ — 6105 CH₂ H CCH₃ N NC₆H₅ CCH₃ C₄H₉ c-C₃H₅ — 6106 CH₂ H CCH₃ N NC₆H₅ CCH₃ CH₃ C₃H₇ — 6107 CH₂ H CCH₃ N NC₆H₅ CCH₃ C₂H₅ C₃H₇ — 6108 CH₂ H CCH₃ N NC₆H₅ CCH₃ C₃H₇ C₃H₇ — 6109 CH₂ H CCH₃ N NC₆H₅ CCH₃ C₂H₅ C₄H₉ — 6110 CH₂ H CCH₃ N NC₆H₅ CCH₃ H 4-CH₃O—C₆H₄ — 6111 O H CCH₃ N NC₆H₅ CCH₃ c-C₃H₅ c-C₃H₅ — 6112 O H CCH₃ N NC₆H₅ CCH₃ CH₃ c-C₃H₅ — 6113 O H CCH₃ N NC₆H₅ CCH₃ C₂H₅ c-C₃H₅ — 6114 O H CCH₃ N NC₆H₅ CCH₃ C₃H₇ c-C₃H₅ — 6115 O H CCH₃ N NC₆H₅ CCH₃ C₄H₉ c-C₃H₅ — 6116 O H CCH₃ N NC₆H₅ CCH₃ CH₃ C₃H₇ — 6117 O H CCH₃ N NC₆H₅ CCH₃ C₂H₅ C₃H₇ — 6118 O H CCH₃ N NC₆H₅ CCH₃ C₃H₇ C₃H₇ — 6119 O H CCH₃ N NC₆H₅ CCH₃ C₂H₅ C₄H₉ — 6120 O H CCH₃ N NC₆H₅ CCH₃ H 4-CH₃O—C₆H₄ — 6121 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ c-C₃H₅ c-C₃H₅ — 1222 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ CH₃ c-C₃H₅ — 6123 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ C₂H₅ c-C₃H₅ — 6124 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ C₃H₇ c-C₃H₅ — 6125 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ C₄H₉ c-C₃H₅ — 6126 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ CH₃ C₃H₇ — 6127 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ C₂H₅ C₃H₇ — 6128 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ C₃H₇ C₃H₇ — 6129 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ C₂H₅ C₄H₉ — 6130 CH₂ CH₃ CCH₃ N NC₆H₅ CCH₃ H 4-CH₃O—C₆H₄ —

Key:

a) Where the compound is indicated as an “oil”, spectral data is provided as follows:

Example 6001 spectral data: MS (NH₃-CI): m/e 338 (M+H⁺, 100%).

The methods used in the preparation of the compounds of Table 1 may be used for preparation of many of the compounds of Structure A of Table 7. The preparation of those compounds derived from cycloaddition of compounds with alkynyl-bearing R¹ groups is illustrated by the following examples.

The methods of Schemes 13 and 14 may be used to prepare many of the examples of Structure B and Structure C contained in Table 7, with minor procedural modifications where necessary and use of reagents of the appropriate structure.

EXAMPLE 7409 Preparation of 9-[1-cyclopropyl-1-(3-methyl-isoxazol-5-yl)methyl]-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine

To a stirring solution of the compound of Example 7241 (90 mg, 0.24 mmol; prepared in a manner similar to that of Example 2 using 6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 3-cyclopropyl-1-propyn-3-ol) in methylene chloride (2 mL) were added chloroacetaldoxime (25 mg, 0.27 mmol) and triethylamine (0.038 mL, 0.27 mmol). (The chloroacetaldoxime used was previously prepared by reacting equimolar amounts of acetaldoxime and N-chlorosuccinimide in DMF, then extracting the product into diethyl ether and washing with water.) The cycloaddition reaction was monitored by TLC and additional amounts of chloroacetaldoxime and triethylamine were added until all the starting material was consumed. The reaction mixture was purified by adding directly to 4 column packed with silica gel and eluting using a gradient of 100% hexane to 25% ethyl acetate in hexane. 72 mg of a white foam was collected. MS (NH₃-CI) 428 (M+H⁺). HRMS: m/e=428.1037 (M+H⁺, C₂₁H₂₀Cl₂N₅O). Purity by reverse phase HPLC>97%.

EXAMPLES 7396 and 7398 Preparation of 6-(2,4-dichlorophenyl)-9-[1-(3-ethoxycarbonyl-isoxazol-5-yl)butyl]-8-ethyl-9H-purine and 9-[1-(4-cyano-3-ethoxycarbonyl-isoxazol-5-yl)butyl]-6-(2,4-dichlorophenyl)-8-ethyl-9H-purine

A solution of the compound of Example 7259 (120 mg, 0.321 mmol; prepared prepared in a manner similar to that of Example 2 using 6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 1-hexyn-3-ol), ethyl chlorooximidoacetate (146 mg, 0.963 mmol) and diisopropylethylamine (170 μL, 0.976 mmol) in toluene (2 mL) was heated to reflux for 20 hours, then cooled and diluted with 20 mL ethyl acetate. This was washed with water (2×20 mL) and satd. aq. brine (20 mL), and the aqueous phases were back-extracted in sequence with ethyl acetate (20 mL). The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and evaporated. The residual material was separated by column chromatography (silica gel, 1:4 ethyl acetate-hexane) to afford, in order, unreacted starting material (about 50 mg) then the compound of Example 7396 (58.7 mg, 0.120 mmol, :37%), and finally the compound of Example 7398 (23.8 mg, 0.046 mmol, 14%), the latter two compounds being amorphous solids. Example 7396 spectral data: TLC R_(F) 0.27 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.67 (1H, d, J=8.1 Hz), 7.58 (1H, d, J=1.8 Hz), 7.41 (1H, dd, J=8.1, 1.8 Hz), 6.86 (1H, s), 5.83 (1H, dd, J=9.9, 6.2 Hz), 4.43 (2H, g, J=7.3 Hz), 2.98 (2H, q, J=7.7 Hz), 2.91-2.78 (1H, m), 2.63-2.49 (1H, m), 1.42 (3H, t, J=7.7 Hz), 1.40 (3H, t, J=7.3 Hz), 1.39-1.19 (2H, m), 1.00 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₃H₂₄Cl₂N₅O₃: 488.1256, found 488.1252; 493 (3), 492 (13), 491 (18), 490 (68), 489 (23), 488 (100). Example 7398 spectral data: TLC R_(F) 0.11 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.99 (1H, s), 7.72 (1H, d, J=8.1 Hz), 7.59 (1H, d, J=1.8 Hz), 7.42 (1H, dd, J=8.1, 1.8 Hz), 5.40 (1H, dd, J=10.4, 5.0 Hz), 4.42 (2H, q, J=7.4 Hz), 3.00-2.90 (2H, m), 2.66-2.52 (1H, m), 2.51-2.38 (1H, m), 1.46 (3H, t, J=7.4 Hz), 1.41 (3H, t, J=7.3 Hz), 1.40-1.10 (2H, m), 0.98 (3H, t, J=7.2 Hz). MS (NH₃-CI): m/e calc'd for C₂₄H₂₅Cl₂N₆O₄: 531.1315, found 531.1315; 531 (100).

TABLE 7

(A)

(B)

(C) m.p., Ex. No. X R⁴ R⁵ R¹¹ R⁶ R^(1a) L G^(a) ° C.^(b) 7001 CH₂ CH₃ CH₃ H CH₃ CH₃ bond G1 — 7002 CH₂ CH₃ CH₃ H CH₃ C₂H₅ bond G1 — 7003 CH₂ CH₃ CH₃ H CH₃ C₃H₇ bond G1 — 7004 CH₂ CH₃ CH₃ H CH₃ c-C₃H₅ bond G1 — 7005 CH₂ CH₃ CH₃ H CH₃ CH₃ bond G2 — 7006 CH₂ CH₃ CH₃ H CH₃ C₂H₅ bond G2 — 7007 CH₂ CH₃ CH₃ H CH₃ C₃H₇ bond G2 — 7008 CH₂ CH₃ CH₃ H CH₃ c-C₃H₅ bond G2 — 7009 CH₂ CH₃ CH₃ H CH₃ CH₃ bond G3 — 7010 CH₂ CH₃ CH₃ H CH₃ C₂H₅ bond G3 — 7011 CH₂ CH₃ CH₃ H CH₃ C₃H₇ bond G3 — 7012 CH₂ CH₃ CH₃ H CH₃ c-C₃H₅ bond G3 — 7013 CH₂ CH₃ CH₃ H CH₃ CH₃ CH₂ G4 — 7014 CH₂ CH₃ CH₃ H CH₃ C₂H₅ CH₂ G4 — 7915 CH₂ CH₃ CH₃ H CH₃ C₃H₇ CH₂ G4 — 7016 CH₂ CH₃ CH₃ H CH₃ c-C₃H₅ CH₂ G4 — 7017 CH₂ CH₃ CH₃ H CH₃ CH₃ CH₂ G5 — 7018 CH₂ CH₃ CH₃ H CH₃ C₂H₅ CH₂ G5 — 7019 CH₂ CH₃ CH₃ H CH₃ C₃H₇ CH₂ G5 — 7020 CH₂ CH₃ CH₃ H CH₃ c-C₃H₅ CH₂ G5 — 7021 CH₂ CH₃ CH₃ H CH₃ CH₃ bond G6 — 7022 CH₂ CH₃ CH₃ H CH₃ C₂H₅ bond G6 — 7023 CH₂ CH₃ CH₃ H CH₃ C₃H₇ bond G6 — 7024 CH₂ CH₃ CH₃ H CH₃ c-C₃H₅ bond G6 — 7025 CH₂ CH₃ CH₃ H CH₃ CH₂═CH bond G7 — 7026 CH₂ CH₃ CH₃ H CH₃ CH₃ bond G8 — 7027 CH₂ CH₃ CH₃ H CH₃ C₂H₅ CH₂ G1 — 7028 CH₂ CH₃ CH₃ H CH₃ C₃H₇ CH₂ G1 — 7029 CH₂ CH₃ CH₃ H CH₃ C₂H₅ CH₂ G2 — 7030 CH₂ CH₃ CH₃ H CH₃ C₃H₇ CH₂ G2 — 7031 CH₂ Cl Cl H H CH₃ bond G1 — 7032 CH₂ Cl Cl H H C₂H₅ bond G1 — 7033 CH₂ Cl Cl H H C₃H₇ bond G1 — 7034 CH₂ Cl Cl H H c-C₃H₅ bond G1 — 7035 CH₂ Cl Cl H H CH₃ bond G2 — 7036 CH₂ Cl Cl H H C₂H₅ bond G2 — 7037 CH₂ Cl Cl H H C₃H₇ bond G2 — 7038 CH₂ Cl Cl H H c-C₃H₅ bond G2 — 7039 CH₂ Cl Cl H H CH₃ bond G3 — 7040 CH₂ Cl Cl H H C₂H₅ bond G3 — 7041 CH₂ Cl Cl H H C₃H₇ bond G3 — 7042 CH₂ Cl Cl H H c-C₃H₅ bond G3 — 7043 CH₂ Cl Cl H H CH₃ CH₂ G4 — 7044 CH₂ Cl Cl H H C₂H₅ CH₂ G4 — 7045 CH₂ Cl Cl H H C₃H₇ CH₂ G4 — 7046 CH₂ Cl Cl H H c-C₃H₅ CH₂ G4 — 7047 CH₂ Cl Cl H H CH₃ CH₂ G5 — 7048 CH₂ Cl Cl H H C₂H₅ CH₂ G5 — 7049 CH₂ Cl Cl H H C₃H₇ CH₂ G5 — 7050 CH₂ Cl Cl H H c-C₃H₅ CH₂ G5 — 7051 CH₂ Cl Cl H H CH₃ bond G6 — 7052 CH₂ Cl Cl H H C₂H₅ bond G6 — 7053 CH₂ Cl Cl H H C₃H₇ bond G6 — 7054 CH₂ Cl Cl H H c-C₃H₅ bond G6 — 7055 CH₂ Cl Cl H H CH₂═CH bond G7 — 7056 CH₂ Cl Cl H H CH₃ bond G8 — 7057 CH₂ Cl Cl H H C₂H₅ CH₂ G1 — 7058 CH₂ Cl Cl H H C₃H₇ CH₂ G1 — 7059 CH₂ Cl Cl H H C₂H₅ CH₂ G2 — 7060 CH₂ Cl Cl H H C₃H₇ CH₂ G2 — 7061 CH₂ CH₃ OCH₃ H H CH₃ bond G1 — 7062 CH₂ CH₃ OCH₃ H H C₂H₅ bond G1 — 7063 CH₂ CH₃ OCH₃ H H C₃H₇ bond G1 — 7064 CH₂ CH₃ OCH₃ H H c-C₃H₅ bond G1 — 7065 CH₂ CH₃ OCH₃ H H CH₃ bond G2 — 7066 CH₂ CH₃ OCH₃ H H C₂H₅ bond G2 — 7067 CH₂ CH₃ OCH₃ H H C₃H₇ bond G2 — 7068 CH₂ CH₃ OCH₃ H H c-C₃H₅ bond G2 — 7069 CH₂ CH₃ OCH₃ H H CH₃ bond G3 — 7070 CH₂ CH₃ OCH₃ H H C₂H₅ bond G3 — 7071 CH₂ CH₃ OCH₃ H H C₃H₇ bond G3 — 7072 CH₂ CH₃ OCH₃ H H c-C₃H₅ bond G3 — 7073 CH₂ CH₃ OCH₃ H H CH₃ CH₂ G4 — 7074 CH₂ CH₃ OCH₃ H H C₂H₅ CH₂ G4 — 7075 CH₂ CH₃ OCH₃ H H C₃H₇ CH₂ G4 — 7076 CH₂ CH₃ OCH₃ H H c-C₃H₅ CH₂ G4 — 7077 CH₂ CH₃ OCH₃ H H CH₃ CH₂ G5 — 7078 CH₂ CH₃ OCH₃ H H C₂H₅ CH₂ G5 — 7079 CH₂ CH₃ OCH₃ H H C₃H₇ CH₂ G5 — 7080 CH₂ CH₃ OCH₃ H H c-C₃H₅ CH₂ C5 — 7081 CH₂ CH₃ OCH₃ H H CH₃ bond G6 — 7082 CH₂ CH₃ OCH₃ H H C₂H₅ bond G6 — 7083 CH₂ CH₃ OCH₃ H H C₃H₇ bond G6 — 7084 CH₂ CH₃ OCH₃ H H c-C₃H₅ bond G6 — 7085 CH₂ CH₃ OCH₃ H H CH₂═CH bond G7 — 7086 CH₂ CH₃ OCH₃ H H CH₃ bond G8 oil 7087 CH₂ CH₃ OCH₃ H H C₂H₅ CH₂ G1 — 7088 CH₂ CH₃ OCH₃ H H C₃H₇ CH₂ G1 — 7089 CH₂ CH₃ OCH₃ H H C₂H₅ CH₂ G2 — 7090 CH₂ CH₃ OCH₃ H H C₃H₇ CH₂ G2 — 7091 CH₂ Cl OCH₃ H H CH₃ bond G1 — 7092 CH₂ Cl OCH₃ H H C₂H₅ bond G1 — 7093 CH₂ Cl OCH₃ H H C₃H₇ bond G1 — 7094 CH₂ Cl OCH₃ H H c-C₃H₅ bond G1 — 7095 CH₂ Cl OCH₃ H H CH₃ bond G2 — 7096 CH₂ Cl OCH₃ H H C₂H₅ bond G2 — 7097 CH₂ Cl OCH₃ H H C₃H₇ bond G2 — 7098 CH₂ Cl OCH₃ H H c-C₃H₅ bond G2 — 7099 CH₂ Cl OCH₃ H H CH₃ bond G3 — 7100 CH₂ Cl OCH₃ H H C₂H₅ bond G3 — 7101 CH₂ Cl OCH₃ H H C₃H₇ bond G3 — 7102 CH₂ Cl OCH₃ H H c-C₃H₅ bond G3 — 7103 CH₂ Cl OCH₃ H H CH₃ CH₂ G4 — 7104 CH₂ Cl OCH₃ H H C₂H₅ CH₂ G4 — 7105 CH₂ Cl OCH₃ H H C₃H₇ CH₂ G4 — 7106 CH₂ Cl OCH₃ H H c-C₃H₅ CH₂ G4 — 7107 CH₂ Cl OCH₃ H H CH₃ CH₂ G5 — 7108 CH₂ Cl OCH₃ H H C₂H₅ CH₂ G5 — 7109 CH₂ Cl OCH₃ H H C₃H₇ CH₂ G5 — 7110 CH₂ Cl OCH₃ H H c-C₃H₅ CH₂ G5 — 7111 CH₂ Cl OCH₃ H H CH₃ bond G6 — 7112 CH₂ Cl OCH₃ H H C₂H₅ bond G6 — 7113 CH₂ Cl OCH₃ H H C₃H₇ bond G6 — 7114 CH₂ Cl OCH₃ H H c-C₃H₅ bond G6 — 7115 CH₂ Cl OCH₃ H H CH₂═CH bond G7 — 7116 CH₂ Cl OCH₃ H H CH₃ bond G8 oil 7117 CH₂ Cl OCH₃ H H C₂H₅ CH₂ G1 — 7118 CH₂ Cl OCH₃ H H C₃H₇ CH₂ G1 — 7119 CH₂ Cl OCH₃ H H C₂H₅ CH₂ G2 — 7120 CH₂ Cl OCH₃ H H C₃H₇ CH₂ G2 — 7121 CH₂ Cl CF₃ H H CH₃ bond G1 — 7122 CH₂ Cl CF₃ H H C₂H₅ bond G1 — 7123 CH₂ Cl CF₃ H H C₃H₇ bond G1 — 7124 CH₂ Cl CF₃ H H c-C₃H₅ bond G1 — 7125 CH₂ Cl CF₃ H H CH₃ bond G2 — 7126 CH₂ Cl CF₃ H H C₂H₅ bond G2 — 7127 CH₂ Cl CF₃ H H C₃H₇ bond G2 — 7128 CH₂ Cl CF₃ H H c-C₃H₅ bond G2 — 7129 CH₂ Cl CF₃ H H CH₃ bond G3 — 7130 CH₂ Cl CF₃ H H C₂H₅ bond G3 — 7131 CH₂ Cl CF₃ H H C₃H₇ bond G3 — 7132 CH₂ Cl CF₃ H H c-C₃H₅ bond G3 — 7133 CH₂ Cl CF₃ H H CH₃ CH₂ G4 — 7134 CH₂ Cl CF₃ H H C₂H₅ CH₂ G4 — 7135 CH₂ Cl CF₃ H H C₃H₇ CH₂ G4 — 7136 CH₂ Cl CF₃ H H c-C₃H₅ CH₂ G4 — 7137 CH₂ Cl CF₃ H H CH₃ CH₂ G5 — 7138 CH₂ Cl CF₃ H H C₂H₅ CH₂ G5 — 7139 CH₂ Cl CF₃ H H C₃H₇ CH₂ G5 — 7140 CH₂ Cl CF₃ H H c-C₃H₅ CH₂ G5 — 7141 CH₂ Cl CF₃ H H CH₃ bond G6 — 7142 CH₂ Cl CF₃ H H C₂H₅ bond G6 — 7143 CH₂ Cl CF₃ H H C₃H₇ bond G6 — 7144 CH₂ Cl CF₃ H H c-C₃H₅ bond G6 — 7145 CH₂ Cl CF₃ H H CH₂═CH bond G7 — 7146 CH₂ Cl CF₃ H H CH₃ bond G8 oil 7147 CH₂ Cl CF₃ H H C₂H₅ CH₂ G1 — 7148 CH₂ Cl CF₃ H H C₃H₇ CH₂ G1 — 7149 CH₂ Cl CF₃ H H C₂H₅ CH₂ G2 — 7150 CH₂ Cl CF₃ H H C₃H₇ CH₂ G2 — 7151 CH₂ CF₃ Cl H H CH₃ bond G1 — 7152 CH₂ CF₃ Cl H H C₂H₅ bond G1 — 7153 CH₂ CF₃ Cl H H C₃H₇ bond G1 — 7154 CH₂ CF₃ Cl H H c-C₃H₅ bond G1 — 7155 CH₂ CF₃ Cl H H CH₃ bond G2 — 7156 CH₂ CF₃ Cl H H C₂H₅ bond G2 — 7157 CH₂ CF₃ Cl H H C₃H₇ bond G2 — 7158 CH₂ CF₃ Cl H H c-C₃H₅ bond G2 — 7159 CH₂ CF₃ Cl H H CH₃ bond G3 — 7160 CH₂ CF₃ Cl H H C₂H₅ bond G3 — 7161 CH₂ CF₃ Cl H H C₃H₇ bond G3 — 7162 CH₂ CF₃ Cl H H c-C₃H₅ bond G3 — 7163 CH₂ CF₃ Cl H H CH₃ CH₂ G4 — 7164 CH₂ CF₃ Cl H H C₂H₅ CH₂ G4 — 7165 CH₂ CF₃ Cl H H C₃H₇ CH₂ G4 — 7166 CH₂ CF₃ Cl H H c-C₃H₅ CH₂ G4 — 7167 CH₂ CF₃ Cl H H CH₃ CH₂ G5 — 7168 CH₂ CF₃ Cl H H C₂H₅ CH₂ G5 — 7169 CH₂ CF₃ Cl H H C₃H₇ CH₂ G5 — 7170 CH₂ CF₃ Cl H H c-C₃H₅ CH₂ G5 — 7171 CH₂ CF₃ Cl H H CH₃ bond G6 — 7172 CH₂ CF₃ Cl H H C₂H₅ bond G6 — 7173 CH₂ CF₃ Cl H H C₃H₇ bond G6 — 7174 CH₂ CF₃ Cl H H c-C₃H₅ bond G6 — 7175 CH₂ CF₃ Cl H H CH₂═CH bond G7 — 7176 CH₂ CF₃ Cl H H CH₃ bond G8 — 7177 CH₂ CF₃ Cl H H C₂H₅ CH₂ G1 — 7178 CH₂ CF₃ Cl H H C₃H₇ CH₂ G1 — 7179 CH₂ CF₃ Cl H H C₂H₅ CH₂ G2 — 7180 CH₂ CF₃ Cl H H C₃H₇ CH₂ G2 — 7181 CH₂ CH₃ OCH₃ CH₃ H CH₃ bond G1 — 7182 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ bond G1 — 7183 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ bond G1 — 7184 CH₂ CH₃ OCH₃ CH₃ H c-C₃H₅ bond G1 — 7185 CH₂ CH₃ OCH₃ CH₃ H CH₃ bond G2 — 7186 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ bond G2 — 7187 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ bond G2 — 7188 CH₂ CH₃ OCH₃ CH₃ H c-C₃H₅ bond G2 — 7189 CH₂ CH₃ OCH₃ CH₃ H CH₃ bond G3 — 7190 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ bond G3 — 7191 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ bond G3 — 7192 CH₂ CH₃ OCH₃ CH₃ H c-C₃H₅ bond G3 — 7193 CH₂ CH₃ OCH₃ CH₃ H CH₃ CH₂ G4 — 7194 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ CH₂ G4 — 7195 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ CH₂ G4 — 7196 CH₂ CH₃ OCH₃ CH₃ H c-C₃H₅ CH₂ G4 — 7197 CH₂ CH₃ OCH₃ CH₃ H CH₃ CH₂ G5 — 7198 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ CH₂ G5 — 7199 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ CH₂ G5 — 7200 CH₂ CH₃ OCH₃ CH₃ H c-C₃H₅ CH₂ G5 — 7201 CH₂ CH₃ OCH₃ CH₃ H CH₃ bond G6 — 7202 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ bond G6 — 7203 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ bond G6 — 7204 CH₂ CH₃ OCH₃ CH₃ H c-C₃H₅ bond G6 — 7205 CH₂ CH₃ OCH₃ CH₃ H CH₂═CH bond G7 — 7206 CH₂ CH₃ OCH₃ CH₃ H CH₃ bond G8 — 7207 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ CH₂ G1 — 7208 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ CH₂ G1 — 7209 CH₂ CH₃ OCH₃ CH₃ H C₂H₅ CH₂ G2 — 7210 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ CH₂ G2 — 7211 O Cl CF₃ H H C₂H₅ CH₂ G1 — 7212 O Cl CF₃ H H C₃H₇ CH₂ G1 — 7213 O Cl CF₃ H H C₂H₅ bond G2 — 7214 O Cl CF₃ H H C₃H₇ bond G2 — 7215 O Cl CF₃ H H C₂H₅ CH₂ G4 — 7216 CH₂ Cl CF₃ H H C₂H₅ CH₂ G1 — 7217 CH₂ Cl CF₃ H H C₃H₇ CH₂ G1 — 7218 CH₂ Cl CF₃ H H C₂H₅ bond G2 — 7219 CH₂ Cl CF₃ H H C₃H₇ bond G2 — 7220 CH₂ Cl CF₃ H H C₂H₅ CH₂ G4 — 7221 O CF₃ Cl H H C₂H₅ CH₂ G1 — 7222 O CF₃ Cl H H C₃H₇ CH₂ G1 — 7223 O CF₃ Cl H H C₂H₅ bond G2 — 7224 O CF₃ Cl H H C₃H₇ bond G2 — 7225 O CF₃ Cl H H C₂H₅ CH₂ G4 — 7226 CH₂ CF₃ Cl H H C₂H₅ CH₂ G1 — 7227 CH₂ CF₃ Cl H H C₃H₇ CH₂ G1 — 7228 CH₂ CF₃ Cl H H C₂H₅ bond G2 — 7229 CH₂ CF₃ Cl H H C₃H₇ bond G2 — 7230 CH₂ CF₃ Cl H H C₂H₅ CH₂ G4 — 7231 CH₂ CH₃ CH₃ H CH₃ C₂H₅ CH₂O G3 oil 7232 CH₂ Cl Cl H H c-C₃H₅ bond G9 — 7233 O Cl Cl H H c-C₃H₅ bond G9 — 7234 CH₂ Cl CF₃ H H c-C₃H₅ bond G9 oil 7235 O Cl CF₃ H H c-C₃H₅ bond G9 — 7236 CH₂ Cl OCH₃ H H c-C₃H₅ bond G9 — 7237 CH₂ Cl OCF₃ H H c-C₃H₅ bond G9 — 7238 CH₂ CH₃ OCH₃ Cl H c-C₃H₅ bond G9 — 7239 CH₂ Cl Cl H CH₃ c-C₃H₅ bond G9 — 7240 CH₂ CF₃ OCH₃ H H c-C₃H₅ bond G9 — 7241 CH₂ Cl Cl H H c-C₃H₅ bond G10 oil 7242 O Cl Cl H H c-C₃H₅ bond G10 — 7243 CH₂ Cl CF₃ H H c-C₃H₅ bond G10 oil 7244 O Cl CF₃ H H c-C₃H₅ bond G10 — 7245 CH₂ Cl OCH₃ H H c-C₃H₅ bond G10 — 7246 CH₂ Cl OCF₃ H H c-C₃H₅ bond G10 — 7247 CH₂ CH₃ OCH₃ Cl H c-C₃H₅ bond G10 — 7248 CH₂ Cl Cl H CH₃ c-C₃H₅ bond G10 — 7249 CH₂ CF₃ OCH₃ H H c-C₃H₅ bond G10 oil 7250 CH₂ Cl Cl H H C₂H₅ bond G10 oi1 7251 O Cl Cl H H C₂H₅ bond G10 — 7252 CH₂ Cl CF₃ H H C₂H₅ bond G10 98-99 7253 O Cl CF₃ H H C₂H₅ bond G10 — 7254 CH₂ Cl OCH₃ H H C₂H₅ bond G10 — 7255 CH₂ Cl OCF₃ H H C₂H₅ bond G10 — 7256 CH₂ CH₃ OCH₃ Cl H C₂H₅ bond G10 — 7257 CH₂ Cl Cl H CH₃ C₂H₅ bond G10 — 7258 CH₂ CF₃ OCH₃ H H C₂H₅ bond G10 — 7259 CH₂ Cl Cl H H C₃H₇ bond G10 oil 7260 O Cl Cl H H C₃H₇ bond G10 — 7261 CH₂ Cl CF₃ H H C₃H₇ bond G10 oil 7262 O Cl CF₃ H H C₃H₇ bond G10 — 7263 CH₂ Cl OCH₃ H H C₃H₇ bond G10 — 7264 CH₂ Cl OCF₃ H H C₃H₇ bond G10 — 7265 CH₂ CH₃ OCH₃ Cl H C₃H₇ bond G10 — 7266 CH₂ Cl Cl H CH₃ C₃H₇ bond G10 oil 7267 CH₂ CF₃ OCH₃ H H C₃H₇ bond G10 — 7268 CH₂ Cl Cl H H C₅H₁₁ bond G10 oil 7269 O Cl Cl H H C₅H₁₁ bond G10 — 7270 CH₂ Cl CF₃ H H C₅H₁₁ bond G10 oil 7271 O Cl CF₃ H H C₅H₁₁ bond G10 — 7272 CH₂ Cl OCH₃ H H C₅H₁₁ bond G10 — 7273 CH₂ Cl OCF₃ H H C₅H₁₁ bond G10 — 7274 CH₂ CH₃ OCH₃ Cl H C₅H₁₁ bond G10 — 7275 CH₂ Cl Cl H CH₃ C₅H₁₁ bond G10 — 7276 CH₂ CF₃ OCH₃ H H C₅H₁₁ bond G10 — 7277 CH₂ Cl Cl H H CH₃ CH₂ G10 — 7278 O Cl Cl H H CH₃ CH₂ G10 — 7279 CH₂ Cl CF₃ H H CH₃ CH₂ G10 oil 7280 O Cl CF₃ H H CH₃ CH₂ G10 — 7281 CH₂ Cl OCH₃ H H CH₃ CH₂ G10 — 7282 CH₂ Cl OCF₃ H H CH₃ CH₂ G10 — 7283 CH₂ CH₃ OCH₃ Cl H CH₃ CH₂ G10 — 7284 CH₂ Cl Cl H CH₃ CH₃ CH₂ G10 — 7285 CH₂ CF₃ OCH₃ H H CH₃ CH₂ G10 — 7286 CH₂ Cl Cl H H c-C₃H₅ bond G11 oil 7287 O Cl Cl H H c-C₃H₅ bond G11 — 7288 CH₂ Cl CF₃ H H c-C₃H₅ bond G11 oil 7289 O Cl CF₃ H H c-C₃H₅ bond G11 — 7290 CH₂ Cl OCH₃ H H c-C₃H₅ bond G11 — 7291 CH₂ Cl OCF₃ H H c-C₃H₅ bond G11 — 7292 CH₂ CH₃ OCH₃ Cl H c-C₃H₅ bond G11 — 7291 CH₂ Cl Cl H CH₃ c-C₃H₅ bond Gl1 — 7294 CH₂ CF₃ OCH₃ H H c-C₃H₅ bond G11 — 7295 CH₂ Cl Cl H H C₂H₅ bond G11 oil 7296 O Cl Cl H H C₂H₅ bond G11 — 7297 CH₂ Cl CF₃ H H C₂H₅ bond G11 oil 7298 O Cl CF₃ H H C₂H₅ bond G11 — 7299 CH₂ Cl OCH₃ H H C₂H₅ bond G11 — 7300 CH₂ Cl OCF₃ H H C₂H₅ bond G11 — 7301 CH₂ CH₃ OCH₃ Cl H C₂H₅ bond G11 — 7302 CH₂ Cl Cl H CH₃ C₂H₅ bond G11 — 7303 CH₂ CF₃ OCH₃ H H C₂H₅ bond G11 — 7304 CH₂ Cl Cl H H C₃H₇ bond G11 88-89 7305 O Cl Cl H H C₃H₇ bond G11 — 7306 CH₂ Cl CF₃ H H C₃H₇ bond G11 oil 7307 O Cl CF₃ H H C₃H₇ bond G11 — 7308 CH₂ Cl OCH₃ H H C₃H₇ bond G11 — 7309 CH₂ Cl OCF₃ H H C₃H₇ bond G11 — 7310 CH₂ CH₃ OCH₃ Cl H C₃H₇ bond G11 — 7311 CH₂ Cl Cl H CH₃ C₃H₇ bond G11 — 7312 CH₂ CF₃ OCH₃ H H C₃H₇ bond G11 — 7313 CH₂ Cl Cl H H C₆H₅ bond G11 156-157 7314 O Cl Cl H H C₆H₅ bond G11 — 7315 CH₂ Cl CF₃ H H C₆H₅ bond G11 150-151 7316 O Cl CF₃ H H C₆H₅ bond G11 — 7317 CH₂ Cl OCH₃ H H C₆H₅ bond G11 — 7318 CH₂ Cl OCF₃ H H C₆H₅ bond G11 — 7319 CH₂ CH₃ OCH₃ Cl H C₆H₅ bond G11 — 7320 CH₂ Cl Cl H CH₃ C₆H₅ bond G11 — 7321 CH₂ CF₃ OCH₃ H H C₆H₅ bond G11 — 7322 CH₂ Cl Cl H H C₂H₅ bond G12 — 7323 O Cl Cl H H C₂H₅ bond G12 — 7324 CH₂ Cl CF₃ H H C₂H₅ bond G12 oil 7325 O Cl CF₃ H H C₂H₅ bond G12 — 7326 CH₂ Cl OCH₃ H H C₂H₅ bond G12 — 7327 CH₂ Cl OCF₃ H H C₂H₅ bond G12 — 7328 CH₂ CH₃ OCH₃ Cl H C₂H₅ bond G12 — 7329 CH₂ Cl Cl H CH₃ C₂H₅ bond G12 — 7330 CH₂ CF₃ OCH₃ H H C₂H₅ bond G12 — 7331 CH₂ Cl Cl H H C₃H₇ bond G12 — 7332 O Cl Cl H H C₃H₇ bond G12 — 7333 CH₂ Cl CF₃ H H C₃H₇ bond G12 — 7334 O Cl CF₃ H H C₃H₇ bond G12 — 7335 CH₂ Cl OCH₃ H H C₃H₇ bond G12 — 7336 CH₂ Cl OCF₃ H H C₃H₇ bond G12 — 7337 CH₂ CH₃ OCH₃ Cl H C₃H₇ bond G12 — 7338 CH₂ Cl Cl H CH₃ C₃H₇ bond G12 — 7339 CH₂ CF₃ OCH₃ H H C₃H₇ bond G12 — 7340 CH₂ Cl Cl H H c-C₃H₅ bond G12 — 7341 O Cl Cl H H c-C₃H₅ bond G12 — 7342 CH₂ Cl CF₃ H H c-C₃H₅ bond G12 128-130 7343 O Cl CF₃ H H c-C₃H₅ bond G12 — 7344 CH₂ Cl OCH₃ H H c-C₃H₅ bond G12 — 7345 CH₂ Cl OCF₃ H H c-C₃H₅ bond G12 — 7346 CH₂ CH₃ OCH₃ Cl H c-C₃H₅ bond G12 — 7347 CH₂ Cl Cl H CH₃ c-C₃H₅ bond G12 — 7348 CH₂ CF₃ OCH₃ H H c-C₃H₅ bond G12 — 7349 CH₂ Cl CF₃ H H c-C₃H₅ bond G13 oil 7350 CH₂ Cl Cl H H c-C₃H₅ bond G13 — 7351 CH₂ Cl CF₃ H H c-C₃H₅ bond G7 oil 7352 CH₂ Cl Cl H H c-C₃H₅ bond G7 oil 7353 CH₂ Cl CF₃ H H CH₃ bond G7 — 7354 CH₂ Cl Cl H H CH₃ bond C7 — 7355 CH₂ CH₃ OCH₃ CH₃ H CH₃ bond G7 oil 7356 CH₂ CH₃ OCH₃ CH₃ H C₃H₇ bond G7 oil 7357 CH₂ CF₃ OCH₃ H H C₃H₇ bond G7 oil 7358 CH₂ CH₃ OCH₃ CH₃ H C₄H₉ bond G7 oil 7359 CH₂ Cl Cl H CH₃ c-C₃H₅ bond G7 156-158 7360 CH₂ CF₃ OCH₃ H H CH₂ bond G8 oil 7361 CH₂ CH₃ OCH₃ OCH₃ H C₂H₅ bond G10 oil 7362 O Cl Cl H H CH₃ bond G1 — 7363 O Cl CF₃ H H CH₃ bond G1 — 7364 CH₂ Cl OCF₃ H H CH₃ bond G1 — 7365 CH₂ CH₃ OCH₃ Cl H CH₃ bond G1 — 7366 CH₂ Cl Cl H CH₃ CH₃ bond G1 — 7367 CH₂ CF₃ OCH₃ H H CH₃ bond G1 — 7368 CH₂ CH₃ OCH₃ F H CH₃ bond G1 — 7369 O Cl Cl H H C₂H₅ bond G1 — 7370 O Cl CF₃ H H C₂H₅ bond G1 — 7371 CH₂ Cl OCF₃ H H C₂H₅ bond G1 — 7372 CH₂ CH₃ OCH₃ Cl H C₂H₅ bond G1 — 7373 CH₂ Cl Cl H CH₃ C₂H₅ bond G1 — 7374 CH₂ CF₃ OCH₃ H H C₂H₅ bond G1 — 7375 CH₂ CH₃ OCH₃ F H C₂H₅ bond G1 — 7376 O Cl Cl H H C₃H₇ bond G1 — 7377 O Cl CF₃ H H C₃H₇ bond G1 — 7378 CH₂ Cl OCF₃ H H C₃H₇ bond G1 — 7379 CH₂ CH₃ OCH₃ Cl H C₃H₇ bond G1 — 7380 CH₂ Cl Cl H CH₃ C₃H₇ bond G1 — 7381 CH₂ CF₃ OCH₃ H H C₃H₇ bond G1 — 7382 CH₂ CH₃ OCH₃ F H C₃H₇ bond G1 — 7383 O Cl Cl H H c-C₃H₅ bond G1 — 7384 O Cl CF₃ H H c-C₃H₅ bond G1 — 7385 CH₂ Cl OCF₃ H H c-C₃H₅ bond G1 — 7386 CH₂ CH₃ OCH₃ Cl H c-C₃H₅ bond G1 — 7387 CH₂ Cl Cl H CH₃ c-C₃H₅ bond G1 — 7388 CH₂ CF₃ OCH₃ H H c-C₃H₅ bond G1 — 7389 CH₂ CH₃ OCH₃ F H c-C₃H₅ bond G1 — 7389 CH₂ Cl CF₃ H H c-C₃H₅ bond G14 oil 7391 CH₂ Cl Cl H H c-C₃H₅ bond G14 — 7391 CH₂ Cl CF₃ H H c-C₃H₅ bond G15 oil 7392 CH₂ Cl Cl H H c-C₃H₅ bond G15 — 7393 CH₂ Cl CF₃ H H c-C₃H₅ bond G16 139-140 7394 CH₂ Cl Cl H H c-C₃H₅ bond G16 — 7395 CH₂ Cl CF₃ H H c-C₃H₅ bond G17 — 7396 CH₂ Cl Cl H H c-C₃H₅ bond G17 oil 7397 CH₂ Cl CF₃ H H c-C₃H₅ bond G18 — 7398 CH₂ Cl Cl H H c-C₃H₅ bond G18 oil 7399 CH₂ Cl Cl H CH₃ CH₃ bond G8 oil 7400 CH₂ Cl CF₃ H H c-C₃H₅ bond G19 — 7401 CH₂ Cl Cl H H c-C₃H₅ bond G19 oil 7402 CH₂ Cl Cl H H c-C₃H₅ bond G20 oil 7403 CH₂ Cl CF₃ H H c-C₃H₅ bond G20 — 7404 CH₂ Cl Cl H H C₄H₉ bond G1 oil 7405 CH₂ Cl Cl H H C₆H₅ C═O C₆H oil 7406 CH₂ Cl Cl H H C₆H₅ C═O G21 oil 7407 CH₂ Cl Cl H H C₆H₅ C═O G22 oil 7408 CH₂ Cl Cl H H 4-F— C═O CH₃ oil C₆H₄CH₂ 7409 CH₂ Cl Cl H H c-C₃H₅ bond G23 oil Key: (a) G groups:

G7 = CH═CH₂ G8 = E—CH═CH—CH₃

G10 = —C≡CH G11 = —C≡CCH₃

(b) Where a compound is indicated as an “oil”, spectral data is provided as follows:

Example 7056 spectral data: MS (ESI): m/e 363 (M+2), 361 (M⁺, 100%).

Example 7086 spectral data: TLC R_(F) 0.25 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.72 (1H, d, J=9.2 Hz), 6.90-6.84 (2H, m), 6.08 (1H, ddq, J=15.4 Hz, 6.6H, 1.4 Hz), 5.67 (1H, dqd, J=15.4 Hz, 6.5H, 1.5 Hz), 5.24 (1H, br pentet, J=7.0 Hz), 3.85 (3H, s), 2.96 (2H, dq, J=7.5, 1.1 Hz), 2.47 (3H, s), 1.81 (3H, d, J=7.0 Hz), 1.73 (3H, dt, J=6.2, 1.3 Hz), 1.41 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 339 (3), 338 (23), 337 (100).

Example 7116 spectral data: TLC R_(F) 0.15 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.68 (1H, d, J=8.4 Hz), 7.09 (1H, d, J=2.6 Hz), 6.96 (1H, dd, J=8.4, 2.6 Hz), 6.09 (1H, ddq, J=15.4 Hz, 6.6H, 1.8 Hz), 5.67 (1H, dqd, J=15.4 Hz, 6.5H, 1.4 Hz), 5.23 (1H, br pentet, J=6.8 Hz), 3.87 (3H, s), 2.98 (2H, q, J=7.5 Hz), 1.82 (3H, d, J=7.0 Hz), 1.73 (3H, dt, J=6.6, 1.3 Hz), 1.40 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 360 (7), 359 (33), 358 (23), 357 (100).

Example 7145 spectral data:: m.p. 78-79° C. TLC R_(F) 0.52 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.01 (1H, s), 7.86-7.81 (2H, m), 7.68 (1H, d, J=8.0 Hz), 6.38 (2H, ddd, J=17.2 Hz, 10.6H, 5.8 Hz), 5.90-5.83 (1H, m), 5.40 (2H, dd, J=10.6, 1.3 Hz), 5.29 (2H, dt, J=17.2, 0.9 Hz), 2.97 (2H, q, J=7.6 Hz), 1.41 (3H, t, J=7.6 Hz). MS (NH₃-CI): m/e 396 (8), 395 (36), 394 (25), 393 (100). Analysis calculated for C₁₉H₁₆ClF₃N₄: C, 58.10; H, 4.12; N, 14.26; found: C, 58.14; H, 4.28; N, 13.74.

Example 7146 spectral data: TLC R_(F) 0.43 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.99 (1H, s), 7.84-7.79 (2H, m), 7.67 (1H, dd, J=8.5, 1.1 Hz), 6.10 (1H, ddq, J=15.4 Hz, 6.8H, 1.8 Hz), 5.70 (1H, dqd, J=15.4 Hz, 6.5H, 1.1 Hz), 5.24 (1H, pentet, J=7.0 Hz), 2.99 (2H, q, J=7.5 Hz), 1.83 (3H, d, J=7.0 Hz), 1.74 (3H, dt, J=6.6, 1.3 Hz), 1.40 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 398 (7), 397 (36), 396 (25), 395 (100).

Example 7231 spectral data: m.p. 78-88° C. TLC R_(F) 0.55 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): Major isomer: δ8.90 (1H, s), 6.95 (2H, s), 4.68-3.05 (6H, m), 3.02-2.92 (2H, m), 2.70-2.55 (2H, m), 2.32 (3H, s), 2.20-2.00 (2H, m), 2.05 (3H, s), 1.96 (3H, s), 1.70-1.45 (4H, m), 1.39 (3H, t, J=7.7 Hz), 0.93 (3H, t, J=7.3 Hz); Minor isomer: δ8.89 (1H, s), 6.95 (2H, s), 4.68-3.05 (6H, m), 3.02-2.92 (2H, m), 2.70-2.55 (2H, m), 2.32 (3H, s), 2.20-2.00 (2H, m), 2.06 (3H, s), 2.01 (3H, s), 1.70-1.45 (4H, m), 1.38 (3H, t, J=7.7 Hz), 0.90 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₅H₃₅N₄O₂: 423.2760, found 423.2748; 425 (5), 424 (29), 423 (100). Analysis calc'd for C₂₅H₃₄N₄O₂.H₂O: C, 68.15; H, 8.24; N, 12.72; found: C, 67.80; H, 7.89; N, 12.24.

Example 7234 spectral data: TLC R_(F) 0.46 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.9(1H, s), 7.87 (1H, d, J=8.0 Hz), 7.83 (1H, s), 7.68 (1H, d, J=8.0 Hz), 6.50 (1H, d, J=3.0 Hz), 5.99 (1H, d, J=3.0 Hz), 5.10 (1H, d, J=10.6 Hz), 2.99-2.79 (2H, m), 2.20 (3H, s), 2.10-2.00 (1H, m), 1.30 (3H, t, J=7.5 Hz), 1.00-0.90 (1H, m), 0.71-0.59 (2H, m), 0.56-0.46 (1H, m). MS (NH₃-CI): m/e 463 (35), 461 (100).

Example 7241 spectral data: MS (NH₃-CI): m/e 371 (M+H⁺, 100%).

Example 7243 spectral data: TLC R_(F) 0.43 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.01 l (1H, s), 7.85 (1H, d, J=8.0 Hz), 7.83 (1H, s), 7.69 (1H, d, J=8.0 Hz), 5.24 (1H, dd, J=8.4, 2.5 Hz), 3.28 (1H, dq, J=15.5, 7.5 Hz), 3.14 (1H, dq, J=15.5, 7.5 Hz), 2.56 (1H, d, J=2.5 Hz), 1.78-1.67 (1H, m), 1.48 (3H, t, J=7.5 Hz), 0.92-0.81 (2H, m), 0.66-0.49 (2H, m). MS (NH₃-CI): m/e calculated for C₂₀H₁₇ClF₃N₄: 405.1094, found 405.1098; 408 (8), 407 (34), 406 (25), 405 (100).

Example 7249 spectral data: TLC R_(F) 0.19 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.93 (1H, s), 7.72 (1H, d, J=8.5 Hz), 7.37 (1H, d, J=2.5 Hz), 7.18 (1H, dd, J=8.5, 2.5 Hz), 5.23 (1H, dd, J=8.1, 2.6 Hz), 3.92 (3H, s), 3.3-3.04 (2H, m), 2.54 (1H, d, J=2.6 Hz), 1.76-1.64 (1H, m), 1.47 (3H, t, J=7.5 Hz), 0.90-0.80 (2H, m), 0.64-0.52 (2H, m). MS (NH₃-CI): m/e calc'd for C₂₁H₂₀F₃N₄O: 401.1603, found 401.1602; 403 (6), 402 (24), 401 (100).

Example 7250 spectral data: TLC R_(F) 0.17 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.01 (1H, s), 7.67 (1H, d, J=8.5 Hz), 7.58 (1H, d, J=1.8 Hz), 7.41 (1H, dd, J=8.5, 1.8 Hz), 5.53 (1H, dt, J=8.0, 2.6 Hz), 3.20 (1H, dq, J=15.8, 7.5 Hz), 3.05 (1H, dq, J=15.8, 7.5 Hz), 2.55 (1H, d, J=2.6 Hz), 2.42-2.29 (1H, m), 2.28-2.15 (1H, m), 1.46 (3H, t, J=7.5 Hz), 1.04 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₁₈H₁₇Cl₂N₄: 359.0830, found 359.0835; 364 (2), 363 (12), 362 (14), 361 (67), 360 (24), 159 (100).

Example 7259 spectral data: TLC R_(F) 0.22 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.01 (1H, s), 7.67 (1H, d, J=8.1 Hz), 7.58 (1H, d, J=1.8 Hz), 7.40 (1H, dd, J=8.1, 1.8 Hz), 5.63 (1H, dt, J=7.9, 2.5 Hz), 3.20 (1H, dq, J=15.7, 7.7 Hz), 3.05 (1H, dq, J=15.7, 7.7 Hz), 2.54 (1H, d, J=2.5 Hz), 2.37-2.24 (1H, m), 2.19-2.06 (1H, m), 1.60-1.45 (1H, m), 1.46 (3H, t, J=7.7 Hz), 1.39-1.25 (1H, m), 0.99 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₁₉H₁₉Cl₂N₄: 373.0987, found 373.0984; 378 (3), 377 (12), 376 (15), 375 (66), 374 (26), 373 (100).

Example 7261 spectral data: TLC R_(F) 0.52 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.03 (1H, s), 7.84 (2H, m), 7.68 (1H, dd, J=7.3, 0.7 Hz), 5.65 (1H, dt, J=8.1, 2.6 Hz), 3.24-3.02 (2H, m), 2.55 (1H, d, J=2.6 Hz), 2.33-2.25 (1H, m), 2.20-2.12 (1H, m), 1.46 (3H, t, J=7.5 Hz), 1.00 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₀H₁₉ClF₃N₄: 407.1250, found 407.1243; 410 (8), 409 (36), 408 (25), 407 (100).

Example 7266 spectral data: TLC R_(F) 0.19 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.01 (1H, d, J=1.5 Hz), 7.38 (1H, d, J=1.8 Hz), 7.24 (1H, d, J=1.8 Hz), 5.70-5.58 (1H, m), 3.24-3.00 (2H, m), 2.55 (1H, d, J=2.5 Hz), 2.40-2.25 (1H, m), 2.20-2.05 (1H, m), 2.10 (3H, d, J=1.8 Hz), 1.62-1.47 (1H, m), 1.43 (3H, t, J=7.5 Hz), 1.42-1.27 (1H, m), 1.00 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₀H₂₁Cl₂N₄: 387.1143, found 387.1144; 392 (3), 391 (12), 390 (16), 389 (66), 388 (27), 387 (100).

Example 7268 spectral data: TLC R_(F) 0.29 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.01 (1H, s), 7.67 (1H, d, J=8.5 Hz), 7.58 (1H, d, J=2.2 Hz), 7.41 (1H, dd, J=8.5, 2.2 Hz), 5.60 (1H, dt, J=7.9, 2.6 Hz), 3.19 (1H, dq, J=15.3, 7.3 Hz), 3.05 (1H, dq, J=15.3, 7.3 Hz), 2.54 (1H, d, J=2.6 Hz), 2.38-2.23 (1H, m), 2.20-2.05 (1H, m), 1.58-1.44 (1H, m), 1.46 (3H, t, J=7.3 Hz), 1.40-1.23 (5H, m), 0.87 (3H, t, J=7.0 Hz). MS (NH₃-CI): m/e calc'd for C₂₁H₂₃Cl₂N₄: 401.1300, found 401.1300; 406 (3), 405 (13), 404 (17), 403 (69), 402 (28), 401 (100).

Example 7270 spectral data: TLC R_(F) 0.60 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.03 (1H, s), 7.84 (2H, m), 7.68 (1H, dd, J=9.1, 0.7 Hz), 5.62 (1H, dt, J=8.1, 2.6 Hz), 3.24-3.02 (2H, m), 2.55 (1H, d, J=2.6 Hz), 2.34-2.27 (1H, m), 2.19-2.13 (1H, m), 1.46 (3H, t, J=7.3 Hz), 1.40-1.25 (6H, m), 0.88 (3H, t, J=7.0 Hz). MS (NH₃-CI): m/e calc'd for C₂₂H₂₃ClF₃N₄: 435.1563, found 435.1566; 438 (9), 437 (36), 436 (27), 435 (100).

Example 7279 spectral data: TLC R_(F) 0.31 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.97 (1H, s), 7.84 (2H, m), 7.68 (1H, d, J=7.7 Hz), 4.74-4.67 (1H, m), 3.45-3.36 (1H, m), 3.03 (2H, q, J=7.7 Hz), 3.00-2.93 (1H, m), 1.93 (1H, t, J=2.7 Hz), 1.86 (3H, d, J=7.0 Hz), 1.43 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 396 (7), 395 (34), 394 (24), 393 (100).

Example 7286 spectral data: TLC R_(F) 0.29 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.97 (1H, s), 7.68 (1H, d, J=8.4 Hz), 7.58 (1H, d, J=1.8 Hz), 7.41 (1H, dd, J=8.4, 1.8 Hz), 5.19 (1H, dq, J=8.4, 2.6 Hz), 3.26 (1H, dq, J=15.7, 7.3 Hz), 3.14 (1H, dq, J=15.7, 7.3 Hz), 1.88 (3H, d, J=2.6 Hz), 1.70-1.60 (1H, m), 1.47 (3H, t, J=7.3 Hz), 0.89-0.78 (2H, m), 0.60-0.43 (2H, m). MS (NH₃-CI): m/e calc'd for C₂₀H₁₉Cl₂N₄: 385.0986, found 385.0992; 390 (3), 389 (12), 388 (15), 387 (66), 386 (26), 385 (100).

Example 7288 spectral data: MS (NH₃-CI): m/e 419 (M+H⁺, 100%).

Example 7295 spectral data: TLC R_(F) 0.19 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.99 (1H, s), 7.67 (1H, d, J=8.4 Hz), 7.57 (1H, d, J=2.2 Hz), 7.40 (1H, dd, J=8.4, 2.2 Hz), 5.49 (1H, tq, J=7.7, 2.2 Hz), 3.19 (1H, dq, J=15.3, 7.7 Hz), 3.05 (1H, dq, J=15.3, 7.7 Hz), 2.26 (1H, dq, J=21.3, 7.7 Hz), 2.13 (1H, dq, J=21.3, 7.7 Hz), 1.87 (3H, d, J=2.2 Hz), 1.45 (3H, t, J=7.7 Hz), 1.01 (3H, t, J=7.7 Hz). MS (NH₃-CI): m/e calc'd for C₁₉H₁₉Cl₂N₄: 373.0987, found 373.0987; 378 (3), 377 (13), 376 (15), 375 (68), 374 (25), 373 (100).

Example 7297 spectral data: TLC R_(F) 0.48 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.01 (1H, s), 7.83 (2H, m), 7.67 (1H, dd, J=7.4, 0.8 Hz), 5.51 (1H, dt, J=8.1, 2.2 Hz), 3.25-3.03 (2H, m), 2.35-2.13 (2H, m), 1.88 (3H, d, J=2.2 Hz), 1.45 (3H, t, J=7.5 Hz), 1.01 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₀H₁₉ClF₃N₄: 407.1250, found 407.1267; 410 (8), 409 (35), 408 (25), 407 (100).

Example 7306 spectral data: MS (NH₃-CI): m/e 421 (M+H⁺, 100%).

Example 7324 spectral data: TLC R_(F) 0.38 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.9 (1H, s), 7.84 (1H, d, J=8.4 Hz), 7.83 (1H, d, J=1.8 Hz), 7.68 (1H, dd, J=8.4, 1.8 Hz), 7.36 (1H, d, J=3 Hz), 6.51 (1H, d, J=5 Hz), 6.39 (1H, dd, J=5, 3 Hz), 5.78 (1H, dd, J=9, 7 Hz), 3.00-2.85 (2H, m), 2.75-2.52 (2H, m), 1.37 (3H, t, J=7.5 Hz), 0.98 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e 439 (1), 438 (8), 437 (34), 436 (26), 435 (100).

Example 7349 spectral data: TLC R_(F) 0.20 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ9.00 (1H, s), 7.87 (1H, d, J=8.0 Hz), 7.83 (1H, s), 7.69 (1H, d, J=8.0 Hz), 5.01 (1H, d, J=10.6 Hz), 2.93 (1H, dq, J=15.9, 7.5 Hz), 2.75 (1H, dq, J=15.9, 7.5 Hz), 2.58 (3H, s), 2.04-1.94 (1H, m), 1.93 (3H, s), 1.33 (3H, t, J=7.5 Hz), 1.32-1.22 (1H, m), 1.00-0.87 (1H, m), 0.74-0.60 (3H, m). MS (NH₃-CI): m/e calculated for C₂₃H₂₂ClF₃N₅O: 476.1465, found 476.1469; 478 (35), 476 (100).

Example 7351 spectral data: TLC R_(F) 0.44 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.9(1H, s), 7.88-7.82 (2H, m), 7.68 (1H, d, J =8.0 Hz), 6.35 (1H, ddd, J=17.2 Hz, 10.6H, 5.1 Hz), 5.33 (1H, br d, J=10.6 Hz), 5.26 (1H, br d, J=17.2 Hz), 4.43-4.37 (1H, m), 3.02-2.90 (2H, m), 1.99-1.89 (1H, m), 1.41 (3H, t, J=7.5 Hz), 0.94-0.84 (1H, m), 0.62-0.52 (2H, m), 0.40-0.30 (1H, m). MS (NH₃-CI): m/e 411 (1), 410 (7), 409 (34), 408 (25), 407 (100).

Example 7352 spectral data: TLC R_(F) 0.13 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.69 (1H, d, J=8.4 Hz), 7.58 (1H, d, J=2.2 Hz), 7.41 (1H, dd, J=8.8, 2.2 Hz), 6.33 (1H, ddd, J=17.2, 10.6, 5.2 Hz), 5.35-5.20 (2H, m), 4.42-4.35 (1H, m), 3.03-2.88 (2H, m), 2.00-1.89 (1H, m), 1.40 (3H, t, J=7.6 Hz), 0.92-0.82 (1H, m), 0.62-0.52 (2H, m), 0.40-0.30 (1H, m). MS (NH₃-CI): m/e calc'd for C₁₉H₁₉Cl₂N₄: 373.1000, found 373.0995; 378 (3), 377 (12), 376 (15), 375 (66), 374 (26), 373 (100).

Example 7355 spectral data: MS (NH₃-CI): m/e 337 (M+H⁺, 100%).

Example 7356 spectral data: MS (NH₃-CI): m/e 365 (M+H⁺, 100%).

Example 7357 spectral data: TLC R_(F) 0.19 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.70 (1H, d, J=8.4 Hz), 7.35 (1H, d, J=2.6 Hz), 7.19 (1H, dd, J=8.4, 2.6 Hz), 6.42 (1H, ddd, J=16.9, 10.3, 6.6 Hz), 5.27 (1H, d, J=10.2 Hz), 5.14 (1H, d, J=17.3 Hz), 5.08-4.99 (1H, m), 3.91 (3H, s), 2.99-2.90 (2H, m), 2.42-2.29 (1H, m), 2.27-2.15 (1H, m), 1.39 (3H, t, J=7.5 Hz), 1.38-1.10 (2H, m), 0.95 (3H, t, J=7.1 Hz). MS (NH₃-CI): m/e calc'd for C₂₁H₂₄F₃N₄O: 405.1915, found 405.1923; 407 (5), 406 (24), 405 (100). Analysis calc'd for C₂₁H₂₃F₃N₄O: C, 62.37; H, 5.73; N, 13.85; found: C, 62.42; H, 5.73; N, 13.48.

Example 7358 spectral data: MS (NH₃-CI): m/e 379 (M+H⁺, 100%).

Example 7360 spectral data: TLC R_(F) 0.13 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.91 (1H, s), 7.68 (1H, d, J=8.8 Hz), 7.35 (1H, d, J=2.6 Hz), 7.16 (1H, dd, J=8.8, 2.6 Hz), 6.15-6.05 (1H, m), 5.73-5.63 (1H, m), 5.28-5.18 (1H, m), 3.91 (3H, s), 2.96 (2H, q, J=7.4 Hz), 1.82 (3H, d, J=7.3 Hz), 1.74 (3H, dt, J=6.6, 1.3 Hz), 1.39 (3H, t, J=7.4 Hz). MS (NH₃-CI): m/e calc'd for C₂₀H₂₂F₃N₄O: 391.1733, found 391.1736; 393 (3), 392 (23), 391 (100).

Example 7361 spectral data: TLC R_(F) 0.43 (50:50 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.42 (1H, s), 6.84 (1H, s), 5.55 (1H, dt, J=5.5, 2.2 Hz), 3.94 (3H, s), 3.92 (3H, s), 3.49-2.98 (2H, m), 2.54 (1H, d, J=2.6 Hz), 2.45 (3H, s), 2.35-2.16 (2H, m), 1.48 (3H, t, J=7.5 Hz), 1.03 (3H, t, J=7.5 Hz). MS (NH₃-CI): m/e calc'd for C₂₁H₂₅N₄O₂: 365.1978, found 365.1966; 367 (6), 366 (24), 365 (100).

Example 7390 spectral data: TLC R_(F) 0.45 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.99 (1H, s), 7.88 (1H, d, J=8.0 Hz), 7.83 (1H, s), 7.69 (1H, d, J=8.0 Hz), 7.30-7.22 (1H, m), 7.07-7.01 (1H, m), 6.99-6.92 (1H, m), 5.25 (1H, d, J=10.2 Hz), 2.97-2.78 (2H, m), 2.23 (1H, br), 1.32 (3H, t, J=7.3 Hz), 1.10-1.00 (1H, m), 0.81-0.71 (1H, m), 0.64-0.54 (1H, m), 0.50-0.40 (1H, m). MS (NH₃-CI): m/e calc'd for C₂₂H₁₉ClF₃N₄S: 463.0971, found 463.0960; 467 (3), 466 (10), 465 (99), 464 (28), 463 (100).

Example 7392 spectral data: TLC R_(F) 0.44 (30:70 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.99 (1h, s), 7.88 (1H, d, J=8.0 Hz), 7.83 (1H, s), 7.68 (1H, d, J=8.0 Hz), 7.30 (1H, br d, J=4.8 Hz), 7.18 (1H, br d, J=4.8 Hz), 6.92 (1H, m), 5.12 (1H, d, J=9.9 Hz), 2.92-2.67 (2H, m), 2.13 (1H, br), 1.28 (3H, t, J=7.5 Hz), 1.08-0.99 (1H, m), 0.79-0.69 (1H, m), 0.55-0.45 (2H, m). MS (NH₃-CI): m/e calculated for C₂₂H₁₉ClF₃N₄S: 463.0971, found 463.0953; 467 (3), 466 (10), 465 (39), 464 (29), 463 (100).

Example 7396 spectral data: TLC R_(F) 0.27 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.96 (1H, s), 7.67 (1H, d, J=8.1 Hz), 7.58 (1H, d, J=1.8 Hz), 7.41 (1H, dd, J=8.1, 1.8 Hz), 6.86 (1H, s), 5.83 (1H, dd, J=9.9, 6.2 Hz), 4.43 (2H, q, J=7.3 Hz), 2.98 (2H, q, J=7.7 Hz), 2.91-2.78 (1H, m), 2.63-2.49 (1H, m), 1.42 (3H, t, J=7.7 Hz), 1.40 (3H, t, J=7.3 Hz), 1.39-1.19 (2H, m), 1.00 (3H, t, J=7.3 Hz). MS (NH₃-CI): m/e calc'd for C₂₃H₂₄Cl₂N₅O₃: 488.1256, found 488.1252; 493 (3), 492 (13), 491 (18), 490 (68), 489 (28), 488 (100).

Example 7398 spectral data: TLC R_(F) 0.11 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.99 (1H, s), 7.72 (1H, d, J=8.1 Hz), 7.59 (1H, d, J=1.8 Hz), 7.42 (1H, dd, J=8.1, 1.8 Hz), 5.40 (1H, dd, J=10.4, 5.0 Hz), 4.42 (2H, q, J=7.4 Hz), 3.00-2.90 (2H, m), 2.66-2.52 (1H, m), 2.51-2.38 (1H, m), 1.46 (3H, t, J=7.4 Hz), 1.41 (3H, t, J=7.3 Hz), 1.40-1.10 (2H, m), 0.98 (3H, t, J=7.2 Hz). MS (NH₃-CI): m/e calc'd for C₂₄H₂₅Cl₂N₆O₄: 531.1315, found 531.1315; 531 (100).

Example 7399 spectral data: TLC R_(F) 0.13 (20:80 ethyl acetate-hexane). ¹H NMR (300 MHz, CDCl₃): δ8.98 (1H, s), 7.38 (1H, d, J=1.8 Hz), 7.23 (1H, d, J=1.8 Hz), 6.15-6.06 (1H, m), 5.76-5.63 (1H, m), 5.26-5.20 (1H, m), 2.96 (2H, q, J=7.4 Hz), 2.10 (3H, s), 1.83 (3H, d, J=7.0 Hz), 1.74 (3H, d, J=6.6 Hz), 1.37 (3H, t, J=7.4 Hz). MS (NH₃-CI): m/e calc'd for C₁₉H₂₁Cl₂N₄: 375.1117, found 375.1123; 380 (2), 379 (12), 378 (15), 377 (66), 376 (26), 375 (100).

Example 7401 spectral data: TLC R_(F) 0.20 (ethyl acetate). ¹H NMR (300 MHz, CDCl₃): δ8.99 (1H, s), 7.71 (1H, d, J=8.4 Hz), 7.58 (1H, d, J=1.8 Hz), 7.41 (1H, dd, J=8.4, 1.8 Hz), 7.11 (1H, d, J=1.1 Hz), 6.87 (1H, d, J=1.1 Hz), 5.41 (1H, d, J=10.3 Hz), 3.34 (3H, s), 3.08 (1H, dq, J=15.8, 7.7 Hz), 2.89 (1H, dq, J=15.8, 7.7 Hz), 2.39-2.25 (1H, m), 1.14 (3H, t, J=7.7 Hz), 1.07-0.97 (1H, m), 0.70-0.58 (2H, m), 0.52-0.42 (1H, m). MS (NH₃-CI): m/e calc'd for C₂₁H₂₁Cl₂N₆: 427.1205, found 427.1196; 429 (66), 427 (1130).

Example 7402 spectral data: MS (NH₃-CI): m/e 424 (M+H⁺, 100%).

Example 7404 spectral data: MS (NH₃-CI): m/e 419 (M+H⁺, 100%).

Example 7405 spectral data: MS (NH₃-CI): m/e 487 (M+H⁺, 100%).

Example 7406 spectral data: MS (NH₃-CI): m/e 501 (M+H⁺, 100%).

Example 7407 spectral data: MS (NH₃-CI): m/e 517 (M+H⁺, 100%).

Example 7408 spectral data: MS (NH₃-CI): m/e 457 (M+H⁺, 100%).

Example 7409 spectral data: MS (NH₃-CI): m/e 429 (M+H⁺, 100%).

UTILITY CR_(F-R)1 Receptor Binding Assay for the Evaluation of Biological Activity

The following is a description of the isolation of cell membranes containing cloned human CR_(F-R)1 receptors for use in the standard binding assay as well as a description of the assay itself.

Messenger RNA was isolated from human hippocampus. The mRNA was reverse transcribed using oligo (dt) 12-18 and the coding region was amplified by PCR from start to stop codons The resulting PCR fragment was cloned into the EcoRV site of pGEMV, from whence the insert was reclaimed using XhoI+XbaI and cloned into the XhoI+XbaI sites of vector pm3ar (which contains a CMV promoter, the SV40 ‘t’ splice and early poly A signals, an Epstein-Barr viral origin of replication, and a hygromycin selectable marker). The resulting expression vector, called phchCRFR was transfected in 293EBNA cells and cells retaining the episome were selected in the presence of 400 mM hygromycin. Cells surviving 4 weeks of selection in hygromycin were pooled, adapted to growth in suspension and used to generate membranes for the binding assay described below. Individual aliquots containing approximately 1×10⁸ of the suspended cells were then centrifuged to form a pellet and frozen.

For the binding assay a frozen pellet described above containing 293EBNA cells transfected with hCRFR1 receptors is homogenized in 10 mL of ice cold tissue buffer (50 mM HEPES buffer pH 7.0, containing 10 mM MgCl₂, 2 mM EGTA, 1 mg/L aprotinin, 1 mg/mL leupeptin and 1 mg/mL pepstatin). The homogenate is centrifuged at 40,000×g for 12 min and the resulting pellet rehomogenized in 10 mL of tissue buffer. After another centrifugation at 40,000×g for 12 min, the pellet is resuspended to a protein concentration of 360 mg/mL to be used in the assay.

Binding assays are performed in 96 well plates; each well having a 300 mL capacity. To each well is added 50 mL of test drug dilutions (final concentration of drugs range from 10⁻¹⁰ to 10⁻⁵ M), 100 mL of ¹²⁵I-ovine-CRF (¹²⁵I-o-CRF) (final concentration 150 pM) and 150 mL of the cell homogenate described above. Plates are then allowed to incubate at room temperature for 2 hours before filtering the incubate over GF/F filters (presoaked with 0.3% polyethyleneimine) using an appropriate cell harvester. Filters are rinsed 2 times with ice cold assay buffer before removing individual filters and assessing them for radioactivity on a gamma counter.

Curves of the inhibition of ¹²⁵I-o-CRF binding to cell membranes at various dilutions of test drug are analyzed by the iterative curve fitting program LIGAND [P. J. Munson and D. Rodbard, Anal. Biochem. 107:220 (1980), which provides K_(i) values for inhibition which are then used to-assess biological activity.

Alternatively, tissues and cells which naturally express CRF receptors can be employed in binding assays analogous to those described above.

A compound is considered to be active if it has a K_(i) value of less than about 10000 nM for the inhibition of CRF.

Inhibition of CRF-Stimulated Adenylate Cyclase Activity

Inhibition of CRF-stimulated adenylate cyclase activity can be performed as described by G. Battaglia et al. Synapse 1:572 (1987). Briefly, assays are carried out at 37° C. for 10 min in 200 mL of buffer containing 100 mM Tris-HCl (pH 7.4 at 37° C.), 10 mM MgCl₂, 0.4 mM EGTA, 0.1% BSA, 1 mM isobutylmethylxanthine (IBMX), 250 units/mL phosphocreatine kinase, 5 mM creatine phosphate, 100 mM guanosine 5′-triphosphate, 100 nM oCRF, antagonist peptides (concentration range 10⁻⁹ to 10⁻⁶ M) and 0.8 mg original wet weight tissue (approximately 40-60 mg protein). Reactions are initiated by the addition of 1 mM ATP/³²P]ATP (approximately 2-4 mCi/tube) and terminated by the addition of 100 mL of 50 mM Tris-HCL, 45 mM ATP and 2% sodium dodecyl sulfate. In order to monitor the recovery of cAMP, 1 mL of [³H]cAMP (approximately 40,000 dpm) is added to each tube prior to separation. The separation of [³²p]CAMP from [³²P]ATP is performed by sequential elution over Dowex and alumina columns.

In vivo Biological Assay

The in vivo activity of the compounds of the present invention can be assessed using any one of the biological assays available and accepted within the art. Illustrative of these tests include the Acoustic Startle Assay, the Stair Climbing Test, and the Chronic Administration Assay. These and other models useful for the testing of compounds of the present invention have been outlined in C. W. Berridge and A. J. Dunn Brain Research Reviews 15:71 (1990). Compounds may be tested in any species of rodent or small mammal.

Compounds of this invention have utility in the treatment of inbalances associated with abnormal levels of corticotropin releasing factor in patients suffering from depression, affective disorders, and/or anxiety.

Compounds of this invention can be administered to treat these abnormalities by means that produce contact of the active agent with the agent's site of action in the body of a mammal. The compounds can be administered by any conventional means available for use in conjunction with pharmaceuticals either as individual therapeutic agent or in combination of therapeutic agents. They can be administered alone, but will generally be administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice.

The dosage administered will vary depending on the use and known factors such as pharmacodynamic character of the particular agent, and its mode and route of administration; the recipient's age, weight, and health; nature and extent of symptoms; kind of concurrent treatment; frequency of treatment; and desired effect. For use in the treatment of said diseases or conditions, the compounds of this invention can be orally administered daily at a dosage of the active ingredient of 0.002 to 200 mg/kg of body weight. Ordinarily, a dose of 0.01 to 10 mg/kg in divided doses one to four times a day, or in sustained release formulation will be effective in obtaining the desired pharmacological effect.

Dosage forms (compositions) suitable for administration contain from about 1 mg to about 100 mg of active ingredient per unit. In these pharmaceutical compositions, the active ingredient will ordinarily be present in an amount of about 0.5 to 95% by weight based on the total weight of the composition.

The active ingredient can be administered orally is solid dosage forms, such as capsules, tablets and powders; or in liquid forms such as elixirs, syrups, and/or suspensions. The compounds of this invention can also be administered parenterally in sterile liquid dose formulations.

Gelatin capsules can be used to contain the active ingredient and a suitable carrier such as but not limited to lactose, starch, magnesium stearate, steric acid, or cellulose derivatives. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of time. Compressed tablets can be sugar-coated or film-coated to mask any unpleasant taste, or used to protect the active ingredients from the atmosphere, or to allow selective disintegration of the tablet in the gastrointestinal tract.

Liquid dose forms for oral administration can contain coloring or flavoring agents to increase patient acceptance.

In general, water, pharmaceutically acceptable oils, saline, aqueous dextrose (glucose), and related sugar solutions and glycols, such as propylene glycol or polyethylene glycol, are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing agents, and if necessary, butter substances. Antioxidizing agents, such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or in combination, are suitable stabilizing agents. Also used are citric acid and its salts, and EDTA. In addition, parenteral solutions can contain preservatives such as benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol.

Suitable pharmaceutical carriers are described in “Remington's Pharmaceutical Sciences”, A. Osol, a standard reference in the field.

Useful pharmaceutical dosage-forms for administration of the compounds of this invention can be illustrated as follows:

CAPSULES

A large number of units capsules are prepared by filling standard two-piece hard gelatin capsules each with 100 mg of powdered active ingredient, 150 mg lactose, 50 mg cellulose, and 6 mg magnesium stearate.

SOFT GELATIN CAPSULES

A mixture of active ingredient in a digestible oil such as soybean, cottonseed oil, or olive oil is prepared and injected by means of a positive displacement was pumped into gelatin to form soft gelatin capsules containing 100 mg of the active ingredient. The capsules were washed and dried.

TABLETS

A large number of tablets are prepared by conventional procedures so that the dosage unit was 100 mg active ingredient, 0.2 mg of colloidal silicon dioxide, 5 mg of magnesium stearate, 275 mg of microcrystalline cellulose, 11 mg of starch, and 98.8 mg lactose. Appropriate coatings may be applied to increase palatability or delayed adsorption.

The compounds of this invention may also be used as reagents or standards in the biochemical study of neurological function, dysfunction, and disease.

Although the present invention has been described and exemplified in terms of certain preferred embodiments, other embodiments will be apparent to those skilled in the art. The invention is, therefore, not limited to the particular embodiments described and exemplified, but is capable of modification or variation without departing from the spirit of the invention, the full scope of which is delineated by the appended claims. 

What is claimed is:
 1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of formula I:

or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein: A is N and B is C—R⁸, or A is C—R⁷ and B is N; D is selected from the group consisting of an aryl or heteroaryl attached through an unsaturated carbon atom; X is selected from the group consisting of CH—R⁹, N—R¹⁰, O, S(O)_(n) and a bond; n is 0, 1 or 2; R¹ is selected from the group consisting of C₁₋₁₀ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl, C₃₋₈ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, —SO₂—C₁₋₁₀ alkyl, —SO₂—R^(1a), and —SO₂—R^(1b); R¹ is substituted with 0-1 substituents selected from the group consisting of —CN, —S(O)_(n)R^(14b), —COR^(13a), —CO₂R^(13a), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —CONR^(13a)R^(16a), 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, and C₃₋₈ cycloalkyl, wherein 0-1 carbon atoms in the C₄₋₈ cycloalkyl is replaced by a group selected from the group consisting of —O—, —S(O)_(n)—, —NR^(13a)—, —NCO₂R^(14b)—, —NCOR^(14b)— and —NSO₂R^(14b)—, and wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group consisting of R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); R¹ is also substituted with 0-3 substituents independently selected at each occurrence from the group consisting of R^(1a), R^(1b), R^(1c), C₁₋₆ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —OR^(13a), —NR^(13a)R^(16a), C₁₋₄ alkoxy-C₁₋₄ alkyl, and C₃₋₈ cycloalkyl which is substituted with 0-1 R⁹ and in which 0-1 carbons of C₄₋₈ cycloalkyl is replaced by —O—; provided that R¹ is other than: (a) a cyclohexyl-(CH₂)₂— group; (b) a 3-cyclopropyl-3-methoxypropyl group; (c) an unsubstituted-(alkoxy)methyl group; and, (d) a 1-hydroxyalkyl group; also provided that when R¹ alkyl substituted with OH, then the carbon adjacent to the ring N is other than CH₂; R^(1a) is aryl and is selected from the group consisting of phenyl, naphthyl, indanyl and indenyl, each R^(1a) being substituted with 0-1 —OR¹⁷ and 0-5 substituents independently selected at each occurrence from the group consisting of C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a); R^(1b) is heteroaryl and is selected from the group consisting of pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group consisting of C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —OC(O)R¹⁸, —NR^(15a)COR¹⁷, —N(COR¹⁷)₂, —NR^(15a)CONR^(17a)R^(19a), —NR^(15a)CO₂R¹⁸, —NR^(17a)R^(19a), and —CONR^(17a)R^(19a) and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group consisting of R^(15a), CO₂R^(14b), COR^(14b) and SO₂R^(14b); R^(1c) is heterocyclyl and is a saturated or partially saturated heteroaryl, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected at each occurrence from the group consisting of C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR^(13a), SH, —S(O)_(n)R^(14b), —COR^(13a), —OC(O)R^(14b), —NR^(15a)COR^(13a), —N(COR^(13a))₂, —NR^(15a)CONR^(13a)R^(16a), —NR^(15a)CO₂R^(14b), —NR^(13a)R^(16a), and —CONR^(13a)R^(16a) and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group consisting of R^(13a), CO₂R^(14b), COR^(14b) and SO₂R^(14b) and wherein any sulfur atom is optionally monooxidized or dioxidized; provided that R¹ is other than a —(CH₂)₁₋₄-aryl, —(CH₂)₁₋₄-heteroaryl, or —(CH₂)₁₋₄-heterocycle, wherein the aryl, heteroaryl, or heterocycle group is substituted or unsubstituted; R² is selected from the group consisting of C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl and is substituted with 0-3 substituents selected from the group consisting of —CN, hydroxy, halo and C₁₋₄ alkoxy; alternatively R², in the case where X is a bond, is selected from the group consisting of —CN, CF₃ and C₂F₅; R³, R⁷ and R⁸ are independently selected at each occurrence from the group consisting of H, Br, Cl, F, I, —CN, C₁₋₄ alkyl, C₃₋₈ cycloalkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, C₁₋₄ alkylsulfinyl, C₁₋₄ alkylsulfonyl, amino, C₁₋₄ alkylamino, (C₁₋₄ alkyl)₂amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group consisting of C₁₋₇ alkyl, C₃₋₈ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, C₁₋₄ alkylthio, C₁₋₄ alkyl sulfinyl, C₁₋₄ alkylsulfonyl, C₁₋₆ alkylamino and (C₁₋₄ alkyl)₂amino; provided that when R¹ is unsubstituted C₁₋₁₀ alkyl, then R³ is other than substituted or unsubstituted phenyl; R⁹ and R¹⁰ are independently selected at each occurrence from the group consisting of H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl-C₁₋₄ alkyl and C₃₋₈ cycloalkyl; R¹³ is selected from the group consisting of H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl, aryl(C₁₋₄ alkyl)-, heteroaryl and heteroaryl(C₁₋₄ alkyl)-; R^(13a) and R^(16a) are independently selected at each occurrence from the group consisting of H, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl; R¹⁴ is selected from the group consisting of C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, aryl, aryl(C₁₋₄ alkyl)-, heteroaryl and heteroaryl(C₁₋₄ alkyl)- and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group consisting of C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy C₁₋₄ haloalkoxy, and dimethylamino; R^(14a) is selected from the group consisting of C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group consisting of C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino; R^(14b) is selected from the group consisting of C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₃₋₆ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl; R¹⁵ is independently selected at each occurrence from the group consisting of H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, phenyl and benzyl, each phenyl or benzyl being substituted on the aryl moiety with 0-3 groups chosen from the group consisting of C₁₋₄ alkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, nitro, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, and dimethylamino; R^(15a) is independently selected at each occurrence from the group consisting of H, C₁₋₄ alkyl, C₃₋₇ cycloalkyl, and C₃₋₆ cycloalkyl-C₁₋₆ alkyl; R¹⁷ is selected at each occurrence from the group consisting of H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, C₁₋₄ haloalkyl, R¹⁴S(O)_(n)—C₁₋₄ alkyl, and R^(17b)R^(19b)N—C₂₋₄ alkyl; R¹⁸ and R¹⁹ are independently selected at each occurrence from the group consisting of H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl, C₁₋₂ alkoxy-C₁₋₂ alkyl, and C₁₋₄ haloalkyl; alternatively, in an NR¹⁷R¹⁹ moiety, R¹⁷ and R¹⁹ taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group consisting of R¹³, CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴; alternatively, in an NR^(17b)R^(19b) moiety, R^(17b) and R^(19b) taken together form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl, wherein N₄ in 1-piperazinyl is substituted with 0-1 substituents selected from the group consisting of R¹³ , CO₂R¹⁴, COR¹⁴ and SO₂R¹⁴; R^(17a)and R^(19a) are independently selected at each occurrence from the group consisting of H, C₁₋₆ alkyl, C₃₋₁₀ cycloalkyl, C₃₋₆ cycloalkyl-C₁₋₆ alkyl and C₁₋₄ haloalkyl; aryl is independently selected at each occurrence from the group consisting of phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from the group consisting of C₁₋₆ alkyl, C₃₋₆ cycloalkyl, methylenedioxy, C₁₋₄ alkoxy-C₁₋₄ alkoxy, —OR¹⁷, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, —NO₂, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and up to 1 phenyl, each phenyl substituent being substituted with 0-4 substituents selected from the group consisting of C₁₋₃ alkyl, C₁₋₃ alkoxy, Br, Cl, F, I, —CN, dimethylamino, CF₃, C₂F₅, OCF₃, SO₂Me and acetyl; heteroaryl is independently selected at each occurrence from the group consisting of pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-S-oxide, 2,3-dihydrobenzothienyl-S-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted 0-4 carbon atoms with a substituent independently selected at each occurrence from the group consisting of C₁₋₆ alkyl, C₃₋₆ cycloalkyl, Br, Cl, F, I, C₁₋₄ haloalkyl, —CN, nitro, —OR¹⁷, SH, —S(O)_(n)R¹⁸, —COR¹⁷, —CO₂R¹⁷, —OC(O)R¹⁸, —NR¹⁵COR¹⁷, —N(COR¹⁷)₂, —NR¹⁵CONR¹⁷R¹⁹, —NR¹⁵CO₂R¹⁸, —NR¹⁷R¹⁹, and —CONR¹⁷R¹⁹ and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group consisting of R¹⁵, CO₂R^(14a), COR^(14a) and SO₂R^(14a); and, provided that when D is imidazole or triazole, R¹ is other than unsubstituted. C₁₋₆ linear or branched alkyl or C₃₋₆ cycloalkyl.
 2. A method of treating a patient suffering from a disease associated with CRF hypersecretion, comprising administering to said patient a CRF antagonistic amount of a compound according to claim 1, wherein the disease associated with CRF hypersecretion is selected from the group consisting of: major depression, anxiety-related disorders and post-traumatic stress disorder. 